Lin RY, Wang JH, Lu XM, Zhou XT, Mantion G, Wen H, Vuitton DA, Richert L. Components of the mitogen-activated protein kinase cascade are activated in hepatic cells by Echinococcus multilocularis metacestode. World J Gastroenterol 2009; 15(17): 2116-2124 [PMID: 19418584 DOI: 10.3748/wjg.15.2116]
Corresponding Author of This Article
Lysiane Richert, Professor, Laboratoire de Toxicologie Cellulaire, EA 4267, Faculté de Médecine et Pharmacie, University of Franche-Comté, Place Saint-Jacques, 25030 Besançon, France. lysiane.richert@yahoo.com
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World J Gastroenterol. May 7, 2009; 15(17): 2116-2124 Published online May 7, 2009. doi: 10.3748/wjg.15.2116
Components of the mitogen-activated protein kinase cascade are activated in hepatic cells by Echinococcus multilocularis metacestode
Ren-Yong Lin, Jun-Hua Wang, Xiao-Mei Lu, Xiao-Tao Zhou, Georges Mantion, Hao Wen, Dominique A Vuitton, Lysiane Richert
Ren-Yong Lin, Jun-Hua Wang, Xiao-Mei Lu, Xiao-Tao Zhou, Hao Wen, Xinjiang Key Laboratory on Echinococcosis and Liver Surgery, 1st Teaching Hospital of Xinjiang Medical University, No.1 Liyushan Road, Urumqi 830054, China
Ren-Yong Lin, Lysiane Richert, Laboratoire de Toxicologie Cellulaire, EA 4267, Faculté de Médecine et Pharmacie, University of Franche-Comté, Place Saint-Jacques, 25030 Besançon, France
Georges Mantion, Liver Surgery and Transplantation Unit, EA 3921, Department of Digestive Surgery, University Hospital Jean Minjoz, Boulevard Fleming, 25030 Besançon, France; WHO-Collaborating Centre for the Prevention and Treatment of Human Echinococcosis, University of Franche-Comté, Place Saint Jacques, 25030 Besançon, France
Dominique A Vuitton, WHO-Collaborating Centre for the Prevention and Treatment of Human Echinococcosis, University of Franche-Comté, Place Saint Jacques, 25030 Besançon, France
Author contributions: Lin RY originated the study, he performed most of the experimental work, analyzed the data and prepared the figures and the draft versions of the manuscript; Wang JH and Lu XM were involved in the collection, preservation and pathological identification of the human liver samples in Urumqi, China; Zhou XT contributed to the immunostainings and measurements performed on these samples; Mantion G and Wen H, hepatic surgeons, contributed to the design of the study, to the diagnosis, surgical treatment and follow-up of the patients with alveolar echinococcosis and supervised in vivo studies; Vuitton DA contributed to the design of the study, and interpretation of the data; Richert L was much involved in the interpretation of the data and revised all draft versions and the definitive version of the manuscript.
Correspondence to: Lysiane Richert, Professor, Laboratoire de Toxicologie Cellulaire, EA 4267, Faculté de Médecine et Pharmacie, University of Franche-Comté, Place Saint-Jacques, 25030 Besançon, France. lysiane.richert@yahoo.com
Telephone: +33-3-81665553
Fax: +33-3-81665679
Received: January 10, 2009 Revised: March 19, 2009 Accepted: March 26, 2009 Published online: May 7, 2009
Abstract
AIM: To explore the effect of Echinococcus multilocularis (E. multilocularis) on the activation of mitogen-activated protein kinase (MAPK) signaling pathways and on liver cell proliferation.
METHODS: Changes in the phosphorylation of MAPKs and proliferating cell nuclear antigen (PCNA) expression were measured in the liver of patients with alveolar echinococcosis (AE). MAPKs, MEK1/2 [MAPK/extracellular signal-regulated protein kinase (ERK) kinase] and ribosomal S6 kinase (RSK) phosphorylation were detected in primary cultures of rat hepatocytes in contact in vitro with (1) E. multilocularis vesicle fluid (EmF), (2) E. multilocularis-conditioned medium (EmCM).
RESULTS: In the liver of AE patients, ERK 1/2 and p38 MAPK were activated and PCNA expression was increased, especially in the vicinity of the metacestode. Upon exposure to EmF, p38, c-Jun N-terminal kinase (JNK) and ERK1/2 were also activated in hepatocytes in vitro, as well as MEK1/2 and RSK, in the absence of any toxic effect. Upon exposure to EmCM, only JNK was up-regulated.
CONCLUSION: Previous studies have demonstrated an influence of the host on the MAPK cascade in E. multilocularis. Our data suggest that the reverse, i.e. parasite-derived signals efficiently acting on MAPK signaling pathways in host liver cells, is actually operating.
Lin RY, Wang JH, Lu XM, Zhou XT, Mantion G, Wen H, Vuitton DA, Richert L. Components of the mitogen-activated protein kinase cascade are activated in hepatic cells by Echinococcus multilocularis metacestode. World J Gastroenterol 2009; 15(17): 2116-2124 [PMID: 19418584 DOI: 10.3748/wjg.15.2116]
