Steroid Receptor Coactivator 3 Contributes to Host Defense against Enteric Bacteria by Recruiting Neutrophils via Upregulation of CXCL2 Expression.

Wenbo Chen, Xuqiang Lu, Yuan Chen, Ming Li, Pingli Mo, Zhangwei Tong, Wei Wang, Wei Wan, Guoqiang Su, Jianming Xu, Chundong Yu

Journal of immunology (Baltimore, Md. : 1950) 2017 Feb 15

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Steroid receptor coactivator 3 (SRC-3) is a transcriptional coactivator that interacts with nuclear receptors and some other transcription factors to enhance their effects on target gene transcription. We reported previously that SRC-3-deficient (SRC-3-/-) mice are extremely susceptible to Escherichia coli-induced septic peritonitis as a result of uncontrolled inflammation and a defect in bacterial clearance. In this study, we observed significant upregulation of SRC-3 in colonic epithelial cells in response to Citrobacter rodentium infection. Based on these findings, we hypothesized that SRC-3 is involved in host defense against attaching and effacing bacterial infection. We compared the responses of SRC-3-/- and wild-type mice to intestinal C. rodentium infection. We found that SRC-3-/- mice exhibited delayed clearance of C. rodentium and more severe tissue pathology after oral infection with C. rodentium compared with wild-type mice. SRC-3-/- mice expressed normal antimicrobial peptides in the colons but exhibited delayed recruitment of neutrophils into the colonic mucosa. Accordingly, SRC-3-/- mice showed a delayed induction of CXCL2 and CXCL5 in colonic epithelial cells, which are responsible for neutrophil recruitment. At the molecular level, we found that SRC-3 can activate the NF-κB signaling pathway to promote CXCL2 expression at the transcriptional level. Collectively, we show that SRC-3 contributes to host defense against enteric bacteria, at least in part via upregulating CXCL2 expression to recruit neutrophils. Copyright © 2017 by The American Association of Immunologists, Inc.

Citation

Wenbo Chen, Xuqiang Lu, Yuan Chen, Ming Li, Pingli Mo, Zhangwei Tong, Wei Wang, Wei Wan, Guoqiang Su, Jianming Xu, Chundong Yu. Steroid Receptor Coactivator 3 Contributes to Host Defense against Enteric Bacteria by Recruiting Neutrophils via Upregulation of CXCL2 Expression. Journal of immunology (Baltimore, Md. : 1950). 2017 Feb 15;198(4):1606-1615