title: Campylobacter jejuni infection suppressed Cl⁻ secretion induced by CFTR activation in T-84 cells.
abstract: Campylobacter jejuni causes foodborne disease associated with abdominal pain, gastroenteritis, and diarrhea. These symptoms are induced by bacterial adherence and invasion of host epithelial cells. C. jejuni infection can occur with a low infective dose, suggesting that C. jejuni may have evolved strategies to cope with the bacterial clearance system in the gastrointestinal tract. The mucosa layer is the first line of defense against bacteria. Mucus conditions are maintained by water and anion (especially Cl(-)) movement. Cystic fibrosis transmembrane conductance regulator (CFTR) is the main Cl(-) channel transporting Cl(-) to the lumen. Mutations in CFTR result in dehydrated secreted mucus and bacterial accumulation in the lungs, and recent studies suggest that closely related pathogenic bacteria also may survive in the intestine. However, the relationship between C. jejuni infection and CFTR has been little studied. Here, we used an (125)I(-) efflux assay and measurement of short-circuit current to measure Cl(-) secretion in C. jejuni-infected T-84 human intestinal epithelial cells. The basic state of Cl(-) secretion was unchanged by C. jejuni infection, but CFTR activator was observed to induce Cl(-) secretion suppressed in C. jejuni-infected T-84 cells. The suppression of activated Cl(-) secretion was bacterial dose-dependent and duration-dependent. A similar result was observed during infection with other C. jejuni strains. The mechanism of suppression may occur by affecting water movement or mucus condition in the intestinal tract. A failure of mucus barrier function may promote bacterial adhesion or invasion of host intestinal epithelial cells, thereby causing bacterial preservation in the host intestinal tract.
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: c201231009@tokushima-u.ac.jp.
authors.forename: Sachie
authors.initials: S
authors.lastname: Negoro
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: shimohata@nutr.med.tokushima-u.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Shimohata
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: c201331016@tokushima-u.ac.jp.
authors.forename: Syo
authors.initials: S
authors.lastname: Hatayama
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: c201002011@tokushima-u.ac.jp.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: ma11230911@gmail.com.
authors.forename: Mari
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: iba.hitomi@tokushima-u.ac.jp.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Iba
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: aiharam@nutr.med.tokushima-u.ac.jp.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Aihara
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: uebanso@nutr.med.tokushima-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uebanso
authors.affiliation: Department of Therapeutic Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: hamada@nutr.med.tokushima-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan. Electronic address: nisikawa@life.osaka-cu.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishikawa
authors.affiliation: Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-Kita, Izumisano, Osaka 598-8531, Japan. Electronic address: shinji@vet.osakafu-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: mawatari@nutr.med.tokushima-u.ac.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.affiliation: Department of Preventive Environment and Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 3-18-15, Tokushima City, Tokushima 770-8503, Japan. Electronic address: akiratak@nutr.med.tokushima-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002169:Campylobacter Infections / Q000378:metabolism*; D016123:Campylobacter jejuni; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000819:agonists / Q000096:biosynthesis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: C482900:3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone; D001565:Benzoates; C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D053778:Thiazolidines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP
keywords: CFTR; Campylobacter jejuni; Diarrhea; Efflux assay; Short-circuit current