IL-1-BETA REGULATES THE EXPRESSION OF THE GI2-ALPHA GENE VIA LIPID MEDIATORS IN GUINEA-PIG TRACHEAL MUSCLE

When isolated guinea pig muscle preparations were incubated with human recombinant IL 1 beta, mRNA level of Gi2 alpha but not of Gs alpha increased in a time and dose dependent manner. The increase was partially blocked by inhibitors of lipoxygenase (NDGA) and cycleoxygenase (indomethacin) and PAF antagonist (SC47014A), while U46619 (thromboxane A(2) mimetic), LTD(4), 15-HETE and PAF partially mimicked it. The IL-1 beta induced Gi2 alpha expression was almost completely inhibited by anti-phospholipase A(2) antiserum, whereas preimmune serum had no apparent effects. From these observations, we suggest that IL-1 beta first induces the synthesis and release of Type II inflammatory phospholipase A(2), which in turn stimulates the expression of Gi2 alpha gene via production of various lipid mediators. (C) 1994 Academic Press, Inc.