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

Abstract

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.

• Authors: Qiang Chen, Tenghui Chen, Yixiang Xu, Jingwei Zhu, Yuan Jiang, Yang Zhao, Jianming Xu, Chundong Yu
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 9 Pg. 5444-52 (Nov 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20881187 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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