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Schroeder JT, Ehrlich L, Bieneman AP. Basophils induce protumorigenic cytokines from A549 lung adenocarcinoma via mechanisms requiring IgE, galectin-3, and IL-3 priming. J Leukoc Biol 2025; 117:qiae233. [PMID: 39432748 DOI: 10.1093/jleuko/qiae233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 10/18/2024] [Indexed: 10/23/2024] Open
Abstract
Galectin-3 (Gal-3) is implicated in innate immune cell activation in a host of diseases/conditions. We identified a unique response whereby human basophils secrete interleukin (IL)-4/IL-13 when cocultured with A549 cells-lung adenocarcinoma. While displaying parameters consistent with standard IgE-dependent activation, these Gal-3-dependent responses occurred in the absence of specific IgE/allergens and required cell-to-cell contact. We now hypothesize that this mode of activation also impacts A549 function. Our findings show that cytokines are induced in basophil/A549 cocultures that are not detected when either cell is cultured alone, in particular IL-6. As previously shown for IL-4/IL-13, IL-6 production also required cell-to-cell contact and was dependent on A549-Gal-3, as clones deficient of this lectin induced less cytokine. Using culture-derived basophils (CDBAs), we demonstrate that the IL-6 response and production of another tumorigenic factor, vascular endothelial growth factor A (VEGF-A), are induced in CDBA/A549 cocultures but only after passively sensitizing CDBAs with IgE, in a manner similar to IL-4/IL-13. However, IgE-dependent activation of basophils/CDBAs cultured alone failed to induce IL-6/VEGF. Importantly, IL-3-primed basophils, even those fixed with paraformaldehyde, readily induced IL-6/VEGF-A in cocultures, thus verifying that these cytokines are derived from A549. Overall, these results suggest a complex mechanism whereby Gal-3/IgE interactions between IL-3-primed basophils and A549 have the potential to modulate cytokine production by both cells. With Gal-3 implicated not only in many diseases ranging from asthma to cancer, but also in normal physiological conditions, such as wound healing, these findings are predicted to provide insight into the molecular mechanisms by which this lectin (and IgE) functions in these processes.
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Affiliation(s)
- John T Schroeder
- Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, United States
| | - Laurent Ehrlich
- Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, United States
| | - Anja P Bieneman
- Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, United States
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2
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Portacci A, Iorillo I, Maselli L, Amendolara M, Quaranta VN, Dragonieri S, Carpagnano GE. The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review. Curr Issues Mol Biol 2024; 46:4271-4285. [PMID: 38785528 PMCID: PMC11119966 DOI: 10.3390/cimb46050260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 05/25/2024] Open
Abstract
Galectins are a group of β-galactoside-binding proteins with several roles in immune response, cellular adhesion, and inflammation development. Current evidence suggest that these proteins could play a crucial role in many respiratory diseases such as pulmonary fibrosis, lung cancer, and respiratory infections. From this standpoint, an increasing body of evidence have recognized galectins as potential biomarkers involved in several aspects of asthma pathophysiology. Among them, galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-10 (Gal-10) are the most extensively studied in human and animal asthma models. These galectins can affect T helper 2 (Th2) and non-Th2 inflammation, mucus production, airway responsiveness, and bronchial remodeling. Nevertheless, while higher Gal-3 and Gal-9 concentrations are associated with a stronger degree of Th-2 phlogosis, Gal-10, which forms Charcot-Leyden Crystals (CLCs), correlates with sputum eosinophilic count, interleukin-5 (IL-5) production, and immunoglobulin E (IgE) secretion. Finally, several galectins have shown potential in clinical response monitoring after inhaled corticosteroids (ICS) and biologic therapies, confirming their potential role as reliable biomarkers in patients with asthma.
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Affiliation(s)
- Andrea Portacci
- Institute of Respiratory Disease, Department of Translational Biomedicine and Neuroscience, University “Aldo Moro”, 70121 Bari, Italy; (I.I.); (L.M.); (M.A.); (S.D.); (G.E.C.)
| | - Ilaria Iorillo
- Institute of Respiratory Disease, Department of Translational Biomedicine and Neuroscience, University “Aldo Moro”, 70121 Bari, Italy; (I.I.); (L.M.); (M.A.); (S.D.); (G.E.C.)
| | - Leonardo Maselli
- Institute of Respiratory Disease, Department of Translational Biomedicine and Neuroscience, University “Aldo Moro”, 70121 Bari, Italy; (I.I.); (L.M.); (M.A.); (S.D.); (G.E.C.)
| | - Monica Amendolara
- Institute of Respiratory Disease, Department of Translational Biomedicine and Neuroscience, University “Aldo Moro”, 70121 Bari, Italy; (I.I.); (L.M.); (M.A.); (S.D.); (G.E.C.)
| | | | - Silvano Dragonieri
- Institute of Respiratory Disease, Department of Translational Biomedicine and Neuroscience, University “Aldo Moro”, 70121 Bari, Italy; (I.I.); (L.M.); (M.A.); (S.D.); (G.E.C.)
| | - Giovanna Elisiana Carpagnano
- Institute of Respiratory Disease, Department of Translational Biomedicine and Neuroscience, University “Aldo Moro”, 70121 Bari, Italy; (I.I.); (L.M.); (M.A.); (S.D.); (G.E.C.)
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Wang F, Ye J, Zhu W, Ge R, Hu C, Qian Y, Li Y, Peng Z. Galectin-3 Mediates Endotoxin Internalization and Caspase-4/11 Activation in Tubular Epithelials and Macrophages During Sepsis and Sepsis-Associated Acute Kidney Injury. Inflammation 2024; 47:454-468. [PMID: 37979076 DOI: 10.1007/s10753-023-01928-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 10/16/2023] [Accepted: 10/23/2023] [Indexed: 11/19/2023]
Abstract
Besides being recognized by membrane receptor TLR4, lipopolysaccharide (LPS) can also be internalized into the cytosol and activate Caspase-4/11 pyroptotic pathways to further amplify inflammation in sepsis. The objective of this study was to investigate whether Galectin-3 (Gal3) could promote the uptake of LPS by governing RAGE or administering endocytosis, consequently activating Caspase 4/11 and mediating pyroptosis in sepsis-associated acute kidney injury (SA-AKI). By pinpointing Gal3, LPS, and EEA1 (endosome-marker) or LAMP1 (lysosome-marker) respectively, immunofluorescence discovered that Gal3 and LPS were mainly aggregated in early endosomes initially and translocated into lysosomes afterwards. In cells and animal models, Gal3 and the Caspase-4/11 pathways were simultaneously activated, and the overexpression of Gal3 could exacerbate pyroptosis, whereas inhibition of Gal3 or the knockdown of its expression could ameliorate pyroptosis, reduce the pathological changes of SA-AKI and improve the survival of the animals with SA-AKI. Silencing RAGE reduced pyroptosis in primary tubular epithelial cells (PTCs) activated by Gal3 and LPS but not in cells activated by Gal3 and outer membrane vesicles (with LPS inside), whereas pyroptosis in both was reduced by blockade of Gal3, indicating Gal3 promoted pyroptosis through both RAGE-dependent and RAGE-independent pathways. Our investigation further revealed a positive correlation between serum Gal3 and pyroptotic biomarkers IL-1 beta and IL-18 in patients with sepsis, and that serum Gal3 was an independent risk factor for mortality. Through our collective exploration, we unraveled the significant role of Gal3 in the internalization of LPS and the provocation of more intense pyroptosis, thus making it a vital pathogenic factor in SA-AKI and a possible therapeutic target. Gal3 enabled the internalization of endotoxin into endosomes and lysosomes via both RAGE-dependent (A) and RAGE-independent (B) pathways, leading to pyroptosis. The suppression of Gal3 curbed Caspase4/11 noncanonical inflammasomes and diminished sepsis and SA-AKI.
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Affiliation(s)
- Fengyun Wang
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Junwei Ye
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Critical Care Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China
| | - Weiwei Zhu
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Ruiqi Ge
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chang Hu
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yaoyao Qian
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yiming Li
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
| | - Zhiyong Peng
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.
- Clinical Research Center of Hubei Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
- Department of Critical Care Medicine, Center of Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Sotoudeheian M. Galectin-3 and Severity of Liver Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease. Protein Pept Lett 2024; 31:290-304. [PMID: 38715329 DOI: 10.2174/0109298665301698240404061300] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 03/02/2024] [Accepted: 03/21/2024] [Indexed: 08/13/2024]
Abstract
Metabolic dysfunction-associated Fatty Liver Disease (MAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver and hepatic steatosis, which can progress to critical conditions, including Metabolic dysfunction-associated Steatohepatitis (MASH), liver fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Galectin-3, a member of the galectin family of proteins, has been involved in cascades that are responsible for the pathogenesis and progression of liver fibrosis in MAFLD. This review summarizes the present understanding of the role of galectin-3 in the severity of MAFLD and its associated liver fibrosis. The article assesses the underlying role of galectin-3-mediated fibrogenesis, including the triggering of hepatic stellate cells, the regulation of extracellular degradation, and the modulation of immune reactions and responses. It also highlights the assessments of the potential diagnostic and therapeutic implications of galectin-3 in liver fibrosis during MAFLD. Overall, this review provides insights into the multifaceted interaction between galectin-3 and liver fibrosis in MAFLD, which could lead to the development of novel strategies for diagnosis and treatment of this prevalent liver disease.
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Liu H, Hwang SY, Lee SS. Role of Galectin in Cardiovascular Conditions including Cirrhotic Cardiomyopathy. Pharmaceuticals (Basel) 2023; 16:978. [PMID: 37513890 PMCID: PMC10386075 DOI: 10.3390/ph16070978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/27/2023] [Accepted: 07/04/2023] [Indexed: 07/30/2023] Open
Abstract
Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and synthetic liver failure with abnormal structure and function of many substances, including proteins, lipids, hormones, and carbohydrates such as lectins. The second is due to portal hypertension which invariably accompanies cirrhosis. Portal hypertension leads to a leaky, congested gut with resultant endotoxemia and systemic inflammation. This inflammatory phenotype comprises oxidative stress, cellular apoptosis, and inflammatory cell infiltration. Galectins exert all these pro-inflammatory mechanisms across many different tissues and organs, including the heart. Effective therapies for improving cardiac function in patients with cirrhosis are not available. Conventional strategies for other noncirrhotic heart diseases, including vasodilators, are not feasible because of the significant baseline vasodilation in cirrhotic patients. Therefore, exploring new treatment modalities for cirrhotic cardiomyopathy is of great importance. Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest. This review briefly summarizes the physiological and pathophysiological role of galectin and specifically examines its role in cardiac disease processes. We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed.
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Affiliation(s)
- Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
| | - Sang-Youn Hwang
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
- Department of Internal Medicine, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, Republic of Korea
| | - Samuel S Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada
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Poto R, Loffredo S, Marone G, Di Salvatore A, de Paulis A, Schroeder JT, Varricchi G. Basophils beyond allergic and parasitic diseases. Front Immunol 2023; 14:1190034. [PMID: 37205111 PMCID: PMC10185837 DOI: 10.3389/fimmu.2023.1190034] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 04/14/2023] [Indexed: 05/21/2023] Open
Abstract
Basophils bind IgE via FcεRI-αβγ2, which they uniquely share only with mast cells. In doing so, they can rapidly release mediators that are hallmark of allergic disease. This fundamental similarity, along with some morphological features shared by the two cell types, has long brought into question the biological significance that basophils mediate beyond that of mast cells. Unlike mast cells, which mature and reside in tissues, basophils are released into circulation from the bone marrow (constituting 1% of leukocytes), only to infiltrate tissues under specific inflammatory conditions. Evidence is emerging that basophils mediate non-redundant roles in allergic disease and, unsuspectingly, are implicated in a variety of other pathologies [e.g., myocardial infarction, autoimmunity, chronic obstructive pulmonary disease, fibrosis, cancer, etc.]. Recent findings strengthen the notion that these cells mediate protection from parasitic infections, whereas related studies implicate basophils promoting wound healing. Central to these functions is the substantial evidence that human and mouse basophils are increasingly implicated as important sources of IL-4 and IL-13. Nonetheless, much remains unclear regarding the role of basophils in pathology vs. homeostasis. In this review, we discuss the dichotomous (protective and/or harmful) roles of basophils in a wide spectrum of non-allergic disorders.
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Affiliation(s)
- Remo Poto
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy
| | - Stefania Loffredo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (CNR), Naples, Italy
| | - Gianni Marone
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (CNR), Naples, Italy
| | - Antonio Di Salvatore
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Amato de Paulis
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
| | - John T. Schroeder
- Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Gilda Varricchi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
- Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (CNR), Naples, Italy
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Zhan K, Wang L, Lin H, Fang X, Jia H, Ma X. Novel inflammatory biomarkers in the prognosis of COVID-19. Ther Adv Respir Dis 2023; 17:17534666231199679. [PMID: 37727063 PMCID: PMC10515606 DOI: 10.1177/17534666231199679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 08/18/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND The central role of inflammatory progression in the development of Coronavirus disease 2019 (COVID-19), especially in severe cases, is indisputable. However, the role of some novel inflammatory biomarkers in the prognosis of COVID-19 remains controversial. OBJECTIVE To assess the effect of some novel inflammatory biomarkers in the occurrence and prognosis of COVID-19. METHODS We systematically retrieved the studies related to COVID-19 and the inflammatory biomarkers of interest. The data of each biomarker in different groups were extracted, then were categorized and pooled. The standardized mean difference was chosen as an effect size measure to compare the difference between groups. RESULTS A total of 90 studies with 12,059 participants were included in this study. We found higher levels of endocan, PTX3, suPAR, sRAGE, galectin-3, and monocyte distribution width (MDW) in the COVID-19 positive groups compared to the COVID-19 negative groups. No significant differences for suPAR and galectin-3 were detected between the severe group and mild/moderate group of COVID-19. In addition, the deaths usually had higher levels of PTX3, sCD14-ST, suPAR, and MDW at admission compared to the survivors. Furthermore, patients with higher levels of endocan, galectin-3, sCD14-ST, suPAR, and MDW usually developed poorer comprehensive clinical prognoses. CONCLUSIONS In summary, this meta-analysis provides the most up-to-date and comprehensive evidence for the role of the mentioned novel inflammatory biomarkers in the prognosis of COVID-19, especially in evaluating death and other poor prognoses, with most biomarkers showing a better discriminatory ability.
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Affiliation(s)
- Kegang Zhan
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
- College of Public Health, Southwest Medical University, Luzhou, Sichuan, China
| | - Luhan Wang
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hao Lin
- West China School of Clinical Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoyu Fang
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hong Jia
- College of Public Health, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Xiangyu Ma
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
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Poto R, Gambardella AR, Marone G, Schroeder JT, Mattei F, Schiavoni G, Varricchi G. Basophils from allergy to cancer. Front Immunol 2022; 13:1056838. [PMID: 36578500 PMCID: PMC9791102 DOI: 10.3389/fimmu.2022.1056838] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 11/21/2022] [Indexed: 12/14/2022] Open
Abstract
Human basophils, first identified over 140 years ago, account for just 0.5-1% of circulating leukocytes. While this scarcity long hampered basophil studies, innovations during the past 30 years, beginning with their isolation and more recently in the development of mouse models, have markedly advanced our understanding of these cells. Although dissimilarities between human and mouse basophils persist, the overall findings highlight the growing importance of these cells in health and disease. Indeed, studies continue to support basophils as key participants in IgE-mediated reactions, where they infiltrate inflammatory lesions, release pro-inflammatory mediators (histamine, leukotriene C4: LTC4) and regulatory cytokines (IL-4, IL-13) central to the pathogenesis of allergic diseases. Studies now report basophils infiltrating various human cancers where they play diverse roles, either promoting or hampering tumorigenesis. Likewise, this activity bears remarkable similarity to the mounting evidence that basophils facilitate wound healing. In fact, both activities appear linked to the capacity of basophils to secrete IL-4/IL-13, with these cytokines polarizing macrophages toward the M2 phenotype. Basophils also secrete several angiogenic factors (vascular endothelial growth factor: VEGF-A, amphiregulin) consistent with these activities. In this review, we feature these newfound properties with the goal of unraveling the increasing importance of basophils in these diverse pathobiological processes.
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Affiliation(s)
- Remo Poto
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy,Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy,World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy
| | - Adriana Rosa Gambardella
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy,Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
| | - Gianni Marone
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy,World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy,Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy,Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (CNR), Naples, Italy
| | - John T. Schroeder
- Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD, United States
| | - Fabrizio Mattei
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
| | - Giovanna Schiavoni
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy,*Correspondence: Gilda Varricchi, ; Giovanna Schiavoni,
| | - Gilda Varricchi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy,World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy,Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy,Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (CNR), Naples, Italy,*Correspondence: Gilda Varricchi, ; Giovanna Schiavoni,
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Al-Salam S, Kandhan K, Sudhadevi M, Yasin J, Tariq S. Early Doxorubicin Myocardial Injury: Inflammatory, Oxidative Stress, and Apoptotic Role of Galectin-3. Int J Mol Sci 2022; 23:ijms232012479. [PMID: 36293342 PMCID: PMC9604390 DOI: 10.3390/ijms232012479] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/17/2022] [Accepted: 09/30/2022] [Indexed: 12/06/2022] Open
Abstract
Doxorubicin (DOXO) is an effective drug that is used in the treatment of a large number of cancers. Regardless of its important chemotherapeutic characteristics, its usage is restricted because of its serious side effects; the most obvious is cardiotoxicity, which can manifest acutely or years after completion of treatment, leading to left ventricular dysfunction, dilated cardiomyopathy, and heart failure. Galectin 3 (Gal-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. Gal-3 was found to be upregulated in animal models, correlating with heart failure, atherosclerosis, and myocardial infarction. Male C57B6/J and B6.Cg-Lgals3 <tm 1 Poi>/J Gal-3 knockout (KO) mice were used for a mouse model of acute DOXO-induced cardiotoxicity. Mice were given DOXO or vehicle (normal saline), after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for tissue processing, staining, electron microscopy, and enzyme-linked immunosorbent assay (ELISA). There was a significant increase in the heart concentration of Gal-3 in Gal-3 wild type DOXO-treated mice when compared with the sham control. There were significantly higher concentrations of heart cleaved caspase-3, plasma troponin I, plasma lactate dehydrogenase, and plasma creatine kinase in Gal-3 KO DOXO-treated mice than in Gal-3 wild type DOXO-treated mice. Moreover, there were significantly higher heart antioxidant proteins and lower oxidative stress in Gal-3 wild type DOXO-treated mice than in Gal-3 KO DOXO-treated mice. In conclusion, Gal-3 can affect the redox pathways and regulate cell survival and death of the myocardium following acute DOXO injury.
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Affiliation(s)
- Suhail Al-Salam
- Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
- Correspondence:
| | - Karthishwaran Kandhan
- Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Manjusha Sudhadevi
- Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Javed Yasin
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Saeed Tariq
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
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10
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Minic Janicijevic S, Jovanovic IP, Gajovic NM, Jurisevic MM, Debnath M, Arsenijevic NN, Borovcanin MM. Galectin-3 mediated risk of inflammation in stable schizophrenia, with only possible secondary consequences for cognition. World J Psychiatry 2022; 12:1183-1193. [PMID: 36186503 PMCID: PMC9521526 DOI: 10.5498/wjp.v12.i9.1183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/14/2022] [Accepted: 08/11/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Evidence suggests that cytokines cause immune disturbances, shape immunological sequelae later in life, and modulate the risk of schizophrenia (SC). Galectin-3 (Gal-3), a multifaceted molecule of the glycan family, is involved in the formation of the immunological synapse and modulates the signalling pathway and effector functions of T lymphocytes, which are major producers of cytokines. We have previously reported elevated serum Gal-3 levels in stable SC patients. However, Gal-3 as a link between cognitive functioning and inflammation has not yet been investigated in SC.
AIM To investigate the relationship between serum Gal-3 levels and cognitive performance, serum cytokines, and white blood cell count in three-month stably treated SC patients.
METHODS Twenty-seven patients with SC in remission and 18 healthy volunteers participated in this case-control and correlational study. Clinical assessment was performed using the Positive and Negative Syndrome Scale and the Montreal-Cognitive Assessment. The results of previously measured serum levels of Gal-3, interleukin (IL)-33, soluble suppression of tumorigenicity 2 (sST2), tumor necrosis factor-alpha (TNF-α), IL-6 and IL-17 were used for further statistical analyses, and IL-4, IL-23, IL-1β and transforming growth factor-beta (TGF-β) were now additionally measured with a sensitive enzyme-linked immunosorbent assay. The number of leukocytes in the blood and the percentage of neutrophils, lymphocytes, and monocytes were determined with a standardized routine measurement procedure (Sysmex Technology). Statistical analyses were performed using SPSS 20.0 software.
RESULTS We found no correlation between serum Gal-3 levels and cognitive functioning in SC patients. A positive correlation was found between the levels of Gal-3 and TNF-α (r = 0.476; P = 0.012), Gal-3 and IL-23 (r = 0.417; P = 0.031), and Gal-3 and sST2 (r = 0.402; P = 0.038). The binary logistic model, which included all nine cytokines measured in this patient sample, indicated the particular role of Gal-3 and TGF-β in the duration of SC. In the stabilization phase of SC, we observed a moderate and negative correlation between serum Gal-3 levels and leukocytes (r = -0.449; P < 0.019). Additional linear regression analysis showed a positive correlation between Gal-3 expression and risperidone dose (F: 4.467; P < 0.045; r2 = 0.396).
CONCLUSION The combined activity of Gal-3 and proinflammatory cytokines, TGF-β downregulation and lower counts of leukocytes influence the SC duration. Gal-3 likely manifests indirect immunometabolic regulation of cognition in SC.
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Affiliation(s)
| | - Ivan P Jovanovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
| | - Nevena M Gajovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
| | - Milena M Jurisevic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
| | - Monojit Debnath
- Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore 560029, India
| | - Nebojsa N Arsenijevic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
| | - Milica M Borovcanin
- Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
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11
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Sanjurjo L, Broekhuizen EC, Koenen RR, Thijssen VLJL. Galectokines: The Promiscuous Relationship between Galectins and Cytokines. Biomolecules 2022; 12:1286. [PMID: 36139125 PMCID: PMC9496209 DOI: 10.3390/biom12091286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/09/2022] [Accepted: 09/10/2022] [Indexed: 11/16/2022] Open
Abstract
Galectins, a family of glycan-binding proteins, are well-known for their role in shaping the immune microenvironment. They can directly affect the activity and survival of different immune cell subtypes. Recent evidence suggests that galectins also indirectly affect the immune response by binding to members of another immunoregulatory protein family, i.e., cytokines. Such galectin-cytokine heterodimers, here referred to as galectokines, add a new layer of complexity to the regulation of immune homeostasis. Here, we summarize the current knowledge with regard to galectokine formation and function. We describe the known and potential mechanisms by which galectokines can help to shape the immune microenvironment. Finally, the outstanding questions and challenges for future research regarding the role of galectokines in immunomodulation are discussed.
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Affiliation(s)
- Lucía Sanjurjo
- Health Research Institute of Santiago de Compostela (IDIS), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Barcelona Ave., 15782 Santiago de Compostela, Spain
| | - Esmee C. Broekhuizen
- Department of Radiation Oncology, Amsterdam UMC Location VUmc, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Rory R. Koenen
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
| | - Victor L. J. L. Thijssen
- Department of Radiation Oncology, Amsterdam UMC Location VUmc, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Biology & Immunology, 1081 HV Amsterdam, The Netherlands
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12
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Schroeder JT, Bieneman AP. The S1 Subunit of the SARS-CoV-2 Spike Protein Activates Human Monocytes to Produce Cytokines Linked to COVID-19: Relevance to Galectin-3. Front Immunol 2022; 13:831763. [PMID: 35392091 PMCID: PMC8982143 DOI: 10.3389/fimmu.2022.831763] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/02/2022] [Indexed: 12/12/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly evolved into a pandemic –the likes of which has not been experienced in 100 years. While novel vaccines show great efficacy, and therapeutics continue to be developed, the persistence of disease, with the concomitant threat of emergent variants, continues to impose massive health and socioeconomic issues worldwide. Studies show that in susceptible individuals, SARS-CoV-2 infection can rapidly progress toward lung injury and acute respiratory distress syndrome (ARDS), with evidence for an underlying dysregulated innate immune response or cytokine release syndrome (CRS). The mechanisms responsible for this CRS remain poorly understood, yet hyper-inflammatory features were also evident with predecessor viruses within the β-coronaviridae family, namely SARS-CoV-1 and the Middle East Respiratory Syndrome (MERS)-CoV. It is further known that the spike protein (S) of SARS-CoV-2 (as first reported for other β-coronaviruses) possesses a so-called galectin-fold within the N-terminal domain of the S1 subunit (S1-NTD). This fold (or pocket) shows structural homology nearly identical to that of human galectin-3 (Gal-3). In this respect, we have recently shown that Gal-3, when associated with epithelial cells or anchored to a solid phase matrix, facilitates the activation of innate immune cells, including basophils, DC, and monocytes. A synthesis of these findings prompted us to test whether segments of the SARS-CoV-2 spike protein might also activate innate immune cells in a manner similar to that observed in our Gal-3 studies. Indeed, by immobilizing S components onto microtiter wells, we show that only the S1 subunit (with the NTD) activates human monocytes to produce a near identical pattern of cytokines as those reported in COVID-19-related CRS. In contrast, both the S1-CTD/RBD, which binds ACE2, and the S2 subunit (stalk), failed to mediate the same effect. Overall, these findings provide evidence that the SARS-CoV-2 spike protein can activate monocytes for cytokines central to COVID-19, thus providing insight into the innate immune mechanisms underlying the CRS and the potential for therapeutic interventions.
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Affiliation(s)
- John T Schroeder
- The Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD, United States
| | - Anja P Bieneman
- The Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD, United States
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13
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Yoon KT, Liu H, Zhang J, Han S, Lee SS. Galectin-3 inhibits cardiac contractility via a TNFα-dependent mechanism in cirrhotic rats. Clin Mol Hepatol 2022; 28:232-241. [PMID: 34986297 PMCID: PMC9013610 DOI: 10.3350/cmh.2021.0141] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 01/04/2022] [Indexed: 11/28/2022] Open
Abstract
Background/Aims Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy. Methods Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy. Results Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls. Conclusion Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.
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Affiliation(s)
- Ki Tae Yoon
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada.,During these studies, Dr. Yoon was the recipient of a sabbatical leave from Pusan National University Faculty of Medicine, Yangsan Hospital. His current address is: Division of Gastroenterology, Pusan National University, Yangsan Hospital, Yangsan, South Korea
| | - Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
| | - Jing Zhang
- Dept of Hepatology and Infectious Disease, Youan Hospital, Capital Medical University, Beijing, China
| | - Sojung Han
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada.,Current address: Division of Gastroenterology, Dept of Internal Medicine, Uijeongbu Eulji Medical Center, Uijeongbu-si, South Korea
| | - Samuel S Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
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14
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Hou S, Chen D, Liu J, Chen S, Zhang X, Zhang Y, Li M, Pan W, Zhou D, Guan L, Ge J. Profiling and Molecular Mechanism Analysis of Long Non-Coding RNAs and mRNAs in Pulmonary Arterial Hypertension Rat Models. Front Pharmacol 2021; 12:709816. [PMID: 34267668 PMCID: PMC8277419 DOI: 10.3389/fphar.2021.709816] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 06/16/2021] [Indexed: 12/23/2022] Open
Abstract
Pulmonary arterial hypertension (PAH) is an immune-mediated disease with poor prognosis and associated with various inflammatory immune diseases. In fact, its pathogenesis is far from clear. Although long non-coding RNAs (lncRNAs) have been implicated in PAH, the molecular mechanisms remain largely unknown. For the first time, in lungs of monocrotaline-induced PAH rat models, we simultaneously detected the expression profiles of lncRNAs and mRNAs by high-throughput sequencing, and explored their roles with bioinformatics analysis and cell assay to discover more potential pathogenesis about PAH. Our data identified that a total of 559 lncRNAs and 691 mRNAs were differentially expressed in lungs during the pathogenesis of PAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that these dysregulated lncRNAs and mRNAs participated in important biological processes and pathways of PAH, among which inflammatory and immune responses represented the chief enriched pathway. The lncRNA-mRNA co-expression network was developed to uncover the hidden interactions between lncRNAs and mRNAs. Further, the expression levels of lncRNAs (NONRATT018084.2, NONRATT009275.2, NONRATT007865.2, and NONRATT026300.2) and mRNAs (LGALS3, PDGFC, SERPINA1, and NFIL3) were confirmed using quantitative real-time PCR. In the end, lncRNA NONRATT009275.2 could facilitate macrophage polarization to M2 type and be involved in inflammatory immune response. In conclusion, this study provided candidate drug targets and potential roles on lncRNAs in the pathogenesis of PAH, and several key regulatory genes were identified, which laid the initial foundation for further mechanism study in PAH.
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Affiliation(s)
- Shiqiang Hou
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Dandan Chen
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Jie Liu
- Department of Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shasha Chen
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Xiaochun Zhang
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Yuan Zhang
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Mingfei Li
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Wenzhi Pan
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Daxin Zhou
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Lihua Guan
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Junbo Ge
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.,National Clinical Research Center for Interventional Medicine, Shanghai, China
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15
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Li H, Li J, Xiao W, Zhang Y, Lv Y, Yu X, Zheng J. The Therapeutic Potential of Galectin-3 in the Treatment of Intrahepatic Cholangiocarcinoma Patients and Those Compromised With COVID-19. Front Mol Biosci 2021; 8:666054. [PMID: 34109213 PMCID: PMC8180910 DOI: 10.3389/fmolb.2021.666054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/07/2021] [Indexed: 11/13/2022] Open
Abstract
The novel coronavirus pneumonia COVID-19 is characterized by all age susceptibility, which imposes a dramatic threat to the human species all over the world. According to current available data, the cytokine storm appears to be the most life-threatening symptom of severe COVID-19 cases accompanied with lung fibrosis. Galectin-3 (Gal-3), a member of soluble β-galactoside-binding lectin families, has been implicated as a key regulator in various inflammation conditions in addition to its well-documented roles in cancer. The pro-inflammatory activity of Gal-3 in the inflammatory response and lung fibrosis of COVID-19 has been proposed by emerging studies, which suggested that inhibition of Gal-3 may represent a novel treatment approach for COVID-19 patients. Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis. ICC accounts for 10-25% of primary liver cancers with limited therapeutic options, which has higher incidence in Asian countries, particularly in China. Cancer patients, including ICC patients, are highly vulnerable to COVID-19 due to their impaired immune system. It is thus undoubtedly a challenge for our oncology department to establish effective treatment strategies under the influence of the COVID-19 crisis. According to our management procedures in the COVID-19 era, emergency treatment will be applied to ICC patients who are under life-threatening conditions, despite the COVID-19 infection. To the best of our knowledge, the modulatory function of Gal-3 in ICC is still barely explored to date. In order to evaluate the therapeutic potential of Gal-3 for ICC patients or those comprised with COVID-19, we herein report our preliminary investigation into roles of Gal-3 in ICC. Our results exhibited that the expression of Gal-3 was significantly up-regulated in ICC tissues, and a significant correlation was observed between its overexpression and malignant progression of ICC cells. We further discussed the activity and possible molecular mechanisms of Gal-3 in ICC, which may pave the ways for further exploring the possibility of Gal-3 as a potential therapeutic target for treating ICC patients or those with COVID-19-related conditions.
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Affiliation(s)
- Hao Li
- Biliary Tract Surgery Laboratory, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, China.,Hunan Research Center of Biliary Disease, the First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Jianmin Li
- Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Wei Xiao
- Department of Medical Administration, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yujing Zhang
- The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, School of Medicine, Hunan Normal University, Changsha, China
| | - Yuan Lv
- The Key Laboratory of Molecular Epidemiology in Hunan Province, School of Medicine, Hunan Normal University, Changsha, China
| | - Xing Yu
- The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, School of Medicine, Hunan Normal University, Changsha, China
| | - Jiao Zheng
- Department of Drug Clinical Trial, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
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16
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Srejovic IM, Lukic ML. Galectin-3 in T cell-mediated immunopathology and autoimmunity. Immunol Lett 2021; 233:57-67. [PMID: 33753135 DOI: 10.1016/j.imlet.2021.03.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 03/17/2021] [Indexed: 01/05/2023]
Abstract
Galectin-3 (Gal-3) is the only member of galectin family able to form pentamers and heterodimers with chemokines. Its presence in various cells and tissues suggests variety of regulatory functions in physiological conditions, but increasing body of evidence indicates involvement of Gal-3 in pathological cascades of many diseases. Gal-3 exerts different, sometimes opposite, effects in various disorders or in different phases of the same disease. These differences in action of Gal-3 are related to the localization of Gal-3 in the cell, types of receptors through which it acts, or the types of cells that secrete it. As a regulator of immune response and T-cell activity, Gal-3 appears to have important role in development of autoimmunity mediated by T cells. Absence of Gal-3 in C57Bl6 mice favors Th2 mediated inflammatory myocarditis but attenuate fibrosis. Recent data also indicate Gal-3 involvement in development atherosclerosis. In pathogenesis of diabetes type 1 and autoimmune components of diabetes type 2 Gal-3 may have detrimental or protective role depending on its intracellular or extracellular localization. Gal-3 mediates autoimmune hepatic damage through activation of T-cells or natural killer T cells. Gal-3 is an important mediator in neurodevelopment, neuropathology and behavior due to its expression both in neurons and glial cells. All together, assessing the role of Gal-3 in immunopathology and autoimmunity it could be concluded that it is an important participant in pathogenesis, as well as promising monitoring marker and therapeutic target.
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Affiliation(s)
- Ivan M Srejovic
- University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Svetozara Markovica 69, 34000, Kragujevac, Serbia.
| | - Miodrag L Lukic
- University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Svetozara Markovica 69, 34000, Kragujevac, Serbia; University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Svetozara Markovica 69, 34000, Kragujevac, Serbia.
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