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Interleukin-6 Induces S100A9 Expression in Colonic Epithelial Cells through STAT3 Activation in Experimental Ulcerative Colitis

Cited 29 time in Web of Science Cited 78 time in Scopus
Authors

Lee, Min Jeoung; Lee, Jin-Ku; Choi, Ji Won; Lee, Chang-Seok; Sim, Ji Hyun; Cho, Chung-Hyun; Lee, Kwang-Ho; Cho, Ik-Hyun; Chung, Myung-Hee; Kim, Hang-Rae; Ye, Sang-Kyu

Issue Date
2012-09
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, Vol.7 No.9, p. e38801
Abstract
Background: Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs). Although high concentrations of S100A9 protein and interleukin-6 (IL-6) are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs) remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model. Methods: IL-6 and S100A9 expression, signal transducer and activator of transcription 3 (STAT3) phosphorylation, and infiltration of immune cells were analyzed in mice with dextran sulfate sodium (DSS)-induced colitis. The effects of soluble gp130-Fc protein (sgp130Fc) and S100A9 small interfering (si) RNA (si-S100A9) on DSS-induced colitis were evaluated. The molecular mechanism of S100A9 expression was investigated in an IL-6-treated Caco-2 cell line using chromatin immunoprecipitation assays. Results: IL-6 concentrations increased significantly in the colon tissues of DSS-treated mice. sgp130Fc or si-S100A9 administration to DSS-treated mice reduced granulocyte infiltration in CECs and induced the down-regulation of S100A9 and colitis disease activity. Treatment with STAT3 inhibitors upon IL-6 stimulation in the Caco-2 cell line demonstrated that IL-6 mediated S100A9 expression through STAT3 activation. Moreover, we found that phospho-STAT3 binds directly to the S100A9 promoter. S100A9 may recruit immune cells into inflamed colon tissues. Conclusions: Elevated S100A9 expression in CECs mediated by an IL-6/STAT3 signaling cascade may play an important role in the development of colitis.
ISSN
1932-6203
URI
https://hdl.handle.net/10371/191565
DOI
https://doi.org/10.1371/journal.pone.0038801
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  • Department of Medicine
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