Signal transduction of intestinal epithelial cells involved in absorption of botulinum toxin.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24580432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: Tokyo University of Agriculture
• Principal Investigator: NIWA Koichi 東京農業大学, 生物産業学部, 教授 (20301012)
• Co-Investigator(Renkei-kenkyūsha): WATANABE Toshihiro 東京農業大学, 生物産業学部, 教授 (80175695) ; SAGANE Yoshimasa 東京農業大学, 生物産業学部, 教授 (00624660)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ボツリヌス毒素複合体 / 家畜ボツリヌス症 / 小腸上皮細胞 / エンドサイトーシス / 透過性 / MAPキナーゼ / 腸管吸収

Outline of Final Research Achievements

To clarify the mechanisms of absorption of Clostridium botulinum toxin complex (TC) from intestine, cellular signaling and changes in paracellular permeability elicited by TC were examined. An addition of TC caused an increase in paracellular permeability of rat intestinal epithelial IEC-6 cells cultured on a porous membrane of Transwell. TC also activated extracellular signal-regulated kinase (ERK) and p38, members of MAP kinases. The permeability increase induced by TC was abrogated by the p38 inhibitor SB203580. These results indicate that L-TC increases paracellular permeability by activating p38. Because it was observed that TC translocates via transcytosis in experiments with confocal microscopy, we conclude that TC translocates intestinal epithelial cell layers via both intracellular and transcellular pathways.

Free Research Field

細胞生理学、病態生理学