title: Activation of muscarinic cholinoceptor ameliorates tumor necrosis factor-α-induced barrier dysfunction in intestinal epithelial cells.
abstract: Impaired intestinal barrier function is one of the critical issues in inflammatory bowel diseases. The aim of this study is to investigate muscarinic cholinoceptor (mAChR)-mediated signaling for the amelioration of cytokine-induced barrier dysfunction in intestinal epithelium. Rat colon challenged with TNF-α and interferon γ reduced transepithelial electrical resistance (TER). This barrier injury was attenuated by muscarinic stimulation. In HT-29/B6 intestinal epithelial cells, muscarinic stimulation suppressed TNF-α-induced activation of NF-κB signaling and barrier disruption. Finally, muscarinic stimulation promoted the shedding of TNFR1, which would be a mechanism for the attenuation of TNF-α/NF-κB signaling and barrier disruption via mAChR.
authors.affiliation: Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan; Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Md Rafiqul Islam
authors.initials: MR
authors.lastname: Khan
authors.affiliation: Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Junsuke
authors.initials: J
authors.lastname: Uwada
authors.affiliation: Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yazawa
authors.affiliation: Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Md Tariqul
authors.initials: MT
authors.lastname: Islam
authors.affiliation: Institute of Clinical Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Krug
authors.affiliation: Institute of Clinical Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fromm
authors.affiliation: Laboratory of Physiology, Graduate School of Integrated Pharmaceutical and Nutritional Sciences/Institute for Environmental Sciences University of Shizuoka, Shizuoka, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Karaki
authors.affiliation: Laboratory of Physiology, Graduate School of Integrated Pharmaceutical and Nutritional Sciences/Institute for Environmental Sciences University of Shizuoka, Shizuoka, Japan; Division of Health and Nutrition, Sendai Shirayuri Women's College, Sendai, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Laboratory of Physiology, Graduate School of Integrated Pharmaceutical and Nutritional Sciences/Institute for Environmental Sciences University of Shizuoka, Shizuoka, Japan.
authors.forename: Atsukazu
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: Division of Genome Science and Microbiology, University of Fukui, Fukui, Japan.
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Yoshiki
authors.affiliation: Division of Genome Science and Microbiology, University of Fukui, Fukui, Japan.
authors.forename: Kiyonao
authors.initials: K
authors.lastname: Sada
authors.affiliation: Department of Pharmacology, Kanazawa Medical University, Kanazawa, Japan.
authors.forename: Ikunobu
authors.initials: I
authors.lastname: Muramatsu
authors.affiliation: Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Abu Syed Md
authors.initials: AS
authors.lastname: Anisuzzaman
authors.affiliation: Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan. Electronic address: takotago@asahikawa-med.ac.jp.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D011976:Receptors, Muscarinic; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha
keywords: Inflammatory bowel disease (IBD); Intestinal barrier; Intestinal epithelium; Muscarinic acetylcholine receptor; Tumor necrosis factor (TNF)