SIGNALING VIA MHC CLASS-II MOLECULES SELECTIVELY INDUCES IL-1-BETA OVER IL-1 RECEPTOR ANTAGONIST GENE-EXPRESSION

Activation of human monocytes or human monocytic cell lines by several types of stimuli coordinately induces IL-1 beta and its antagonist (IL-1Ra) gene expression; alterations in their balance seem to mediate the inflammatory response. Using the human monocytic cell line THP-1, we report that superantigens, such as staphylococcal enterotoxin A (SEA) and Mycoplasma arthritidis-derived superantigen (MAM) induce an increase in the level of IL-1 beta mRNA without any detectable effect on IL-1Ra mRNA. Unlike MAM-induced IL-1 beta mRNA, SEA-induced IL-1 beta mRNA was adequatly translated into protein. Superantigen-induced gene expression is mediated by signalling, via their receptors, the MHC class II molecules. Thus, it appears that this mode of signalling selectively induces the proinflammatory cytokine IL-1 beta gene expression which, by itself, can have major importance in disease pathology especially in autoimmune diseases. (C) 1994 Academic Press, Inc.