title: Steroid Receptor Coactivator 3 Contributes to Host Defense against Enteric Bacteria by Recruiting Neutrophils via Upregulation of CXCL2 Expression.
abstract: 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.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.|The First Affiliated Hospital of Xiamen University, Xiamen 361001, China; and.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Xuqiang
authors.initials: X
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Pingli
authors.initials: P
authors.lastname: Mo
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Zhangwei
authors.initials: Z
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wan
authors.affiliation: The First Affiliated Hospital of Xiamen University, Xiamen 361001, China; and.
authors.forename: Guoqiang
authors.identifier: 0000-0001-8833-3931
authors.initials: G
authors.lastname: Su
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China; cdyu@xmu.edu.cn.
authors.forename: Chundong
authors.identifier: 0000-0002-4141-8345
authors.initials: C
authors.lastname: Yu
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology; D054426:Chemokine CXCL2 / Q000235:genetics* / Q000276:immunology; D054365:Chemokine CXCL5 / Q000235:genetics / Q000276:immunology; D044082:Citrobacter rodentium / Q000276:immunology; D003092:Colitis / Q000382:microbiology / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D007249:Inflammation; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000276:immunology; D056921:Nuclear Receptor Coactivator 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; D054426:Chemokine CXCL2; D054365:Chemokine CXCL5; C404915:Cxcl2 protein, mouse; C094739:Cxcl5 protein, mouse; D016328:NF-kappa B; D056921:Nuclear Receptor Coactivator 3