Steroid receptor coactivator 3 is required for clearing bacteria and repressing inflammatory response in Escherichia coli-induced septic peritonitis.
Steroid receptor coactivator 3 (SRC-3) is a multifunctional protein that plays an important role in regulation of bacterial LPS-induced inflammation. However, its involvement in host defense against bacterial infection remains unclear. In this study, we used SRC-3 knockout mice to assess the role of SRC-3 in antibacterial defense in Escherichia coli-induced septic peritonitis. After E. coli bacteria were injected i.p., SRC-3-deficient mice exhibited excessive local and systemic inflammatory responses and more severe bacterial burdens, leading to a significantly higher mortality compared with wild-type mice. Peritoneal macrophages of SRC-3-deficient mice showed a decrease in bacterial phagocytosis in culture and an increase in apoptosis, which was consistent with the defective bacterial clearance observed in SRC-3-deficient mice. Accordingly, SRC-3 null macrophages expressed much lower levels of scavenger receptor A, the antioxidant enzyme catalase, and antiapoptotic gene Bcl-2. Collectively, our data demonstrate that SRC-3 is important not only in modulating the local and systemic inflammation but also in intensifying bacterial clearance, which highlights a pivotal role of SRC-3 in the host defense system against bacterial infection.
Chen
Qiang
Q
Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Chen
Tenghui
T
Xu
Yixiang
Y
Zhu
Jingwei
J
Jiang
Yuan
Y
Zhao
Yang
Y
Xu
Jianming
J
Yu
Chundong
C
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000276:immunology*; D010538:Peritonitis / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000235:genetics / Q000276:immunology*; D014162:Transfection
D016207:Cytokines; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3