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.
Chujor
C S
CS
Sandoz Forschungsinstitut, Vienna, Austria.
Klein
L
L
Lam
C
C
D000818:Animals; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D003513:Cycloheximide