Original Article
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World J Gastroenterol. Oct 21, 2014; 20(39): 14420-14429
Published online Oct 21, 2014. doi: 10.3748/wjg.v20.i39.14420
Production of corticotropin-releasing factor and urocortin from human monocyte-derived dendritic cells is stimulated by commensal bacteria in intestine
Shigeo Koido, Toshifumi Ohkusa, Shin Kan, Kazuki Takakura, Keisuke Saito, Hideo Komita, Zensho Ito, Hiroko Kobayashi, Shinichiro Takami, Kan Uchiyama, Hiroshi Arakawa, Masaki Ito, Masato Okamoto, Mikio Kajihara, Sadamu Homma, Hisao Tajiri
Shigeo Koido, Toshifumi Ohkusa, Kazuki Takakura, Keisuke Saito, Zensho Ito, Hiroko Kobayashi, Shinichiro Takami, Kan Uchiyama, Hiroshi Arakawa, Mikio Kajihara, Hisao Tajiri, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Chiba 277-8567, Japan
Shin Kan, Hideo Komita, Masaki Ito, Sadamu Homma, Department of Oncology, The Jikei University School of Medicine, Tokyo 105-8461, Japan
Masato Okamoto, Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo 108-8641, Japan
Author contributions: Koido S, Ohkusa T and Tajiri H designed the research; Koido S, Kan S, Takakura K, Saito K, Komita H, Ito Z, Kobayashi H, Takami S, Uchiyama K, Arakawa H, Ito M, Okamoto M, Kajihara M and Homma S performed the research and analyzed the data; Koido S wrote the paper.
Supported by Grants-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Foundation for the Promotion of Cancer Research and Mitsui Life Social Welfare Foundation
Correspondence to: Shigeo Koido, MD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8564, Japan. shigeo_koido@jikei.ac.jp
Telephone: +81-4-71641111 Fax: +81-4-71633488
Received: February 22, 2014
Revised: April 17, 2014
Accepted: May 25, 2014
Published online: October 21, 2014
Processing time: 240 Days and 10.1 Hours
Abstract

AIM: To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.

METHODS: Human peripheral blood monocyte-derived dendritic cells (MoDCs) were stimulated by commensal bacterial strains, including Escherichia coli, Clostridium clostridioforme, Bacteroides vulgatus (B. vulgatus), Fusobacterium varium (F. varium), and Lactobacillus delbrueckii subsp. bulgaricus. After incubation, corticotropin-releasing factor (CRF) and urocortin 1 (UCN1) mRNA in the cells was examined by real-time reverse transcription polymerase chain reaction. Supernatants from the cells were tested for CRF and UCN1 using an enzyme-linked immunosorbent assay.

RESULTS: Both CRF and UCN1 were significantly augmented by B. vulgatus and F. varium at both the mRNA and protein levels. In particular, B. vulgatus stimulated human MoDCs, resulting in extremely high levels of CRF and UCN1.

CONCLUSION: Stimulation of MoDCs by B. vulgatus and F. varium may be associated with CRF/UCN1-related intestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease.

Keywords: Commensal bacteria; Corticotropin-releasing factor; Dendritic cell; Irritable bowel syndrome; Inflammatory bowel disease; Urocortin

Core tip: Corticotropin-releasing factor (CRF) and urocortin 1 (UCN1) play critical roles in many stress-related intestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease. However, little is known about the pathophysiology of these diseases. To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation, human peripheral blood monocyte-derived dendritic cells were stimulated by commensal bacterial strains. Both CRF and UCN1 were significantly augmented by Bacteroides vulgatus (B. vulgatus) and Fusobacterium varium (F. varium) at both the mRNA and protein levels. Thus, B. vulgatus and F. varium may be associated with stress-related intestinal disorders.