title: Botulinum toxin complex increases paracellular permeability in intestinal epithelial cells via activation of p38 mitogen-activated protein kinase.
abstract: Clostridium botulinum produces a large toxin complex (L-TC) that increases paracellular permeability in intestinal epithelial cells by a mechanism that remains unclear. Here, we show that mitogen-activated protein kinases (MAPKs) are involved in this permeability increase. Paracellular permeability was measured by FITC-dextran flux through a monolayer of rat intestinal epithelial IEC-6 cells, and MAPK activation was estimated from western blots. L-TC of C. botulinum serotype D strain 4947 increased paracellular dextran flux and activated extracellular signal-regulated kinase (ERK), p38, but not c-Jun N-terminal kinase (JNK) in IEC-6 cells. The permeability increase induced by L-TC was abrogated by the p38 inhibitor SB203580. These results indicate that L-TC increases paracellular permeability by activating p38, but not JNK and ERK.
authors.affiliation: Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri, Hokkaido 099-2493, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Miyashita
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Sagane
authors.forename: Ken
authors.initials: K
authors.lastname: Inui
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Keita
authors.initials: K
authors.lastname: Miyata
authors.forename: Tomonori
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Niwa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001905:Botulinum Toxins / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D003911:Dextrans; D004789:Enzyme Activation / Q000187:drug effects*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D007413:Intestinal Mucosa / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D048051:p38 Mitogen-Activated Protein Kinases; D001905:Botulinum Toxins; D016650:Fluorescein-5-isothiocyanate