Control of the expression of a class II major histocompatibility gene (HLA-DR) in various human cell types: down-regulation by IL-1 but not by IL-6, prostaglandin E2, or glucocorticoids.
We have examined the effects of recombinant human IL-1 alpha and IL-1 beta on expression of the gene for the class II major histocompatibility antigen, HLA-DR, and the class I MHC antigen, HLA-B7, induced by natural or recombinant human IFN-gamma in several human cell types. Recombinant hIL-1 alpha and hIL-1 beta antagonized the class II MHC-inducing effect of IFN-gamma in human monocytes and normal skin fibroblasts, and in chondrosarcoma and astrocytoma cell lines. In the presence of IL-1 alpha or IL-1 beta, the induction by IFN-gamma of HLA-DR mRNA, and the expression of the corresponding antigen on the cell surface, were reduced when analysed by dot-blot hybridization and flow cytometry respectively. Nuclear transcription assays showed that IFN-gamma augmented expression of the HLA-DR gene and that IL-1 alpha inhibited this effect. IL-1-mediated inhibition was not observed with IFN-gamma-induced expression of MHC class I mRNA (HLA-B7). Both IL-1 alpha and IL-1 beta induced production of IL-6 mRNA and of PGE2 in these cell types. However, recombinant IL-6 or PGE2 did not inhibit IFN-gamma-induced HLA-DR mRNA expression. Dexamethasone did not inhibit HLA-DR expression in the cells studied but eliminated the inhibitory effect of IL-1 on such expression. The observations suggest that MHC gene expression is influenced by the cytokine network in a complex manner which is different for class I and II genes. Glucocorticoids and PGE2 do not consistently inhibit class II expression.
Watanabe
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Department of Immunology, Syntex Research, Palo Alto, California 94304.
Lee
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Allison
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D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology; D015536:Down-Regulation; D005347:Fibroblasts / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D015793:HLA-B7 Antigen / Q000096:biosynthesis / Q000235:genetics; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000276:immunology
D015793:HLA-B7 Antigen; D006684:HLA-DR Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D003907:Dexamethasone; D007371:Interferon-gamma; D015232:Dinoprostone