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 cyclooxygenase (indomethacin) and PAF antagonist (SC47014A), while U46619 (thromboxane A2 mimetic), LTD4, 15-HETE and PAF partially mimicked it. The IL-1 beta induced Gi2 alpha expression was almost completely inhibited by anti-phospholipase A2 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 A2, which in turn stimulates the expression of Gi2 alpha gene via production of various lipid mediators.