Inhibited Production of iNOS by Murine J774 Macrophages Occurs via aphoP-Regulated Differential Expression of NFκB and AP-1

[摘要] Background.There are no reported data to explain howSalmonellasuppress nitrite ion production in macrophages or whether this phenomenon is unique to typhoidal or non-typhoidal serovars. The aims of this study were, therefore, to investigate these phenomena.Methods. We measured survival ofS. typhimurium14028 and its phoP mutant in murine J774 macrophages, cultured with or without interferon gamma. We compared expression of inducible nitric oxide synthase (iNOS) mRNA and protein, and nitrite ion production and also examined binding of nuclear factorκB (NFκB) and activator protein 1 (AP-1) to macrophage DNA.Results.S. typhimurium14028 inhibited binding of NFκB and AP-1 to DNA in murine J774. A macrophages via an intact phoP regulon. This correlated with increased survival and reduced iNOS expression. Suppression of NFκB activity was ameliorated in macrophages cultured with IFN-γand this correlated with increased expression of iNOS mRNA and nitrite ion production, although IFN-γhad no effect on AP-1/DNA interaction. We show, that with one exception, suppression of iNOS is unique to typhoidal serovars.Conclusion.S. typhimuriuminhibit NFκB and AP-1 interaction with macrophage DNA via the PhoP regulon, this reduces nitrite ion production and is principally associated with typhoidal serovars.

[学科分类] 传染病学