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

Abstract

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.