Role Of Steroid Receptor Coactivator 3 In Escherichia Coli Peritonitis Of Mice And Anti-inflammatory Drug Screening

Steroid receptor coactivator 3(SRC-3)is a multifunctional protein that plays an important role in the regulation of bacterial lipopolysaccharide-induced inflammation. However,its involvement in host defense against bacterial infection remains unclear. Herein we use SRC-3 deficient mice to determine the role of SRC-3 in antibacterial defense in Escherichia coli-induced septic peritonitis.After intraperitonial injection of E.coli,SRC-3 deficient mice exhibited excessive local and systemic inflammatory responses and bacterial burdens that led to significantly increased mortality rate compared to the wild-type control mice.Peritoneal macrophages from SRC-3 deficient mice impaired phagocytosis of E.coli and enhanced apoptosis,which contribute to defects in bacterial clearance.Decreased expressions of scavenger receptor A,antioxidant enzyme catalase,and antiapoptotic genes such as Bcl-2, cIAP-2 and cFLIP_L in SRC-3 deficient macrophages underlie the impaired phagocytosis of E.coli and enhanced apoptosis.Collectively,our data demonstrate that SRC-3 is crucial in not only modulating the local and systemic inflammation but also intensifying the bacterial clearance,which highlight a pivotal role of SRC-3 in the host defense against bacterial infection.In addition,we structured a TNF-α.-luciferase reporter cell line,being as a sensitive,effective,responsive tool to screening anti-inflammatory drug.By using the reporter cell line,a fungal polyketide mycoepoxydiene was found to suppress LPS-induced inflammation in vitro and in vivo.