Steroid receptor coactivator 3 is required for clearing bacteria and repressing inflammatory response in Escherichia coli-induced septic peritonitis

J Immunol. 2010 Nov 1;185(9):5444-52. doi: 10.4049/jimmunol.0903802. Epub 2010 Sep 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Chromatin Immunoprecipitation
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Escherichia coli Infections / genetics
  • Escherichia coli Infections / immunology*
  • Inflammation / genetics
  • Inflammation / immunology*
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Knockout
  • Nuclear Receptor Coactivator 3 / genetics
  • Nuclear Receptor Coactivator 3 / immunology*
  • Peritonitis / genetics
  • Peritonitis / immunology*
  • Phagocytosis / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sepsis / genetics
  • Sepsis / immunology*
  • Transfection


  • Cytokines
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 3