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Stimulation of Cell Migration by Flagellin Through the p38 MAP Kinase Pathway in Cultured Intestinal Epithelial Cells
Author(s) -
Kondo Yutaka,
HigaNakamine Sayomi,
Maeda Noriko,
Toku Seikichi,
Kakinohana Manabu,
Sugahara Kazuhiro,
Kukita Ichiro,
Yamamoto Hideyuki
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25272
Subject(s) - tlr5 , flagellin , microbiology and biotechnology , mapk/erk pathway , protein kinase a , cell migration , p38 mitogen activated protein kinases , hsp27 , biology , kinase , chemistry , signal transduction , cell , receptor , biochemistry , heat shock protein , hsp70 , tlr4 , tlr2 , gene
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. J. Cell. Biochem. 117: 247–258, 2016. © 2015 Wiley Periodicals, Inc.