title: Steroid receptor coactivator-3 differentially regulates the inflammatory             response in peritoneal macrophages.
abstract: Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator that plays an important role in the regulation of cytokine mRNA translation. In the present study, SCR-3 gene knockout mice were used to study the effects of SCR-3 on the regulation of the inflammatory response in peritoneal macrophages induced by lipopolysaccharides (LPS). Peritoneal macrophages (PMs) of SRC-3-/- mice showed a decrease in the release of TNF-α, IL-1β and IL-6, and an increase in the release of IL-10. Furthermore, results of RT-PCR also showed that levels of TNF-α, IL-1β and IL-6 mRNA expression were significantly lower, while the level of IL-10 mRNA expression was higher in the SRC-3-/- mice, compared to those of wild-type mice, following treatment with LPS (p < 0.01). In addition, western blotting revealed that: i) the extent of reduction of the glucocorticoid receptor in PMs from SRC-3-/- mice was significantly lower than that in wild-type mice (p < 0.01); ii) the extent of increase of AP-1 in PMS from SRC-3-/- mice was significantly lower than that in wild-type mice (p < 0.01); iii) the extent of increase of NF-κB p65 in PMs from SRC-3-/- mice was significantly higher than that in wild-type mice (p < 0.01). Collectively, our studies revealed that SRC-3 may play a key role in the maintenance of innate immunity. Furthermore, absence of the SRC-3 protein may result in the partial loss of inflammation and phagocytosis barrier function, including suppression of LPS-induced transcriptional activity, release of TNF-α, IL-1β and IL-6, and obstruction of the function of phagocytes and elimination of bacteria, as well as their production.
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Command Area, Chengdu, Sichuan 610083, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ying-Hai
authors.initials: YH
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Ou
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Dai
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Su
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D056921:Nuclear Receptor Coactivator 3