INTERLEUKIN-12 GENE-EXPRESSION OF MACROPHAGES IS REGULATED BY NITRIC-OXIDE

Interleukin-12 is a heterodimeric cytokine, mainly produced by macroph ages. In our present study we demonstrate that interleukin-12 expressi on is regulated by nitric oxide. Incubation of the macrophage cell lin e IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRN A and nitric oxide production. The concurrent addition of the nitric o xide synthase inhibitor N-G-monomethyl-L-arginine inhibited nitrite pr oduction and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activ ity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitro so-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRN A levels were induced with nitric oxide donors at 1 mu M concentration . We conclude that nitric oxide may exert an autoregulatory and paracr ine control of interleukin-12 gene expression. (C) 1996 Academic Press , Inc.