INDUCTION OF NITRIC-OXIDE AND NITRIC-OXIDE SYNTHASE MESSENGER-RNA BY SILICA AND LIPOPOLYSACCHARIDE IN PMA-PRIMED THP-1 CELLS

Nitric oxide (NO), a nitrogen-free radical, plays an important role in mediating inflammatory reaction and cytotoxicity of tissue. To determ ine whether NO was involved in silica-induced pulmonary tissue damage, we studied the effects of silica on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression by THP-I cells, a monocyt e-like cell line with properties of the pulmonary alveolar macrophage. Experimental results showed that silica elicited a marked stimulation of nitric oxide production in a time-dependent manner by THP-I cells in vitro following the priming of these cells with the phorbol ester P MA. Both nitric oxide synthase inhibitor N-monomethyl-L-arginine (NMMA ) and xanthine oxidase inhibitor allopurinol can partially suppress si lica-induced NO production in PMA-primed THP-I cells. Northern blot an alysis indicated that, after 2 h of silica exposure, PMA-primed THP-I cells began to express iNOS mRNA, which reached peak expression at 8 h . Endotoxin treatment of these cells produced a similar effect. These results indicated that silica is a potent inducer of NO production in macrophages and its ability to induce tissue damage may partially be a ttributed to its ability to initiate excessive production of nitric ox ide from macrophages.