Selective inhibition of interleukin-1 beta gene expression in activated RAW 264.7 macrophages by interferon-gamma.

The ability of interleukin-1 (IL-1) to activate epidermal cell populations supports its role as a key cytokine in the pathogenesis of a number of inflammatory skin diseases. In the present study, we have examined the effect of interferon (IFN)-gamma on the expression of the IL-1 beta gene in mouse RAW 264.7 macrophages activated by lipopolysaccharide (LPS) plus tumor necrosis factor (TNF)-alpha. Incubation of macrophages with both LPS and TNF-alpha resulted in the expression of both IL-1 beta and inducible nitric oxide synthase (iNOS) mRNA transcripts and increased the release of IL-1 beta protein and nitrite production in culture supernatants. Addition of IFN-gamma up-regulated the expression of the iNOS gene in cells activated by LPS + TNF-alpha, but significantly suppressed the induction of IL-1 beta gene expression in a dose-dependent manner. The suppression required neither de novo protein synthesis nor involved destabilization of the mRNA transcripts. Together, these findings suggest that IFN-gamma can be an important regulatory cytokine in a chronic inflammatory site and may explain its purported anti-inflammatory effects in certain dermatological diseases.