title: Stimulation of Cell Migration by Flagellin Through the p38 MAP Kinase Pathway in Cultured Intestinal Epithelial Cells.
abstract: Toll-like receptor 5 (TLR5) is a receptor for flagellin and is present on the basolateral surface of intestinal epithelial cells. However, the pathological roles of TLR5 in intestinal epithelial cells are not clear at present. In previous reports, we demonstrated that treatment of cultured alveolar epithelial cells with flagellin activated the p38 mitogen-activated protein kinase (MAPK) pathway and enhanced epithelial-mesenchymal transition induced by transforming growth factor beta 1 (TGF-β1). In translating our findings in alveolar epithelial cells to intestinal epithelial cells, we found that both flagellin and TGF-β1 activated p38 MAPK and its downstream protein kinase, MAPK-activated protein kinase-2 (MAPKAPK-2) in an IEC-6 intestinal epithelial cell line. The phosphorylation of HSP27, one of the substrates for MAPKAPK-2, was also increased. TGF-β1 increased the protein level of α-smooth muscle actin (αSMA), and flagellin enhanced the effect of TGF-β1. A wound healing assay revealed that flagellin and TGF-β1 stimulated the migration of cells. SB203580, an inhibitor of p38 MAPK, and an inhibitor of MAPKAPK-2 inhibited flagellin-stimulated migration. These results suggested that TLR5 is involved in the migration of intestinal epithelial cells through activation of the p38 MAPK pathway.
authors.affiliation: Department of Emergency Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.|Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Sayomi
authors.initials: S
authors.lastname: Higa-Nakamine
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Seikichi
authors.initials: S
authors.lastname: Toku
authors.affiliation: Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kakinohana
authors.affiliation: Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugahara
authors.affiliation: Department of Emergency Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kukita
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005408:Flagellin / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D005408:Flagellin
keywords: FLAGELLIN; IEC-6 CELLS; INTESTINAL EPITHELIAL CELLS; MIGRATION; TLR5; p38 MAPK