Induction of nitric oxide and nitric oxide synthase mRNA by silica and lipopolysaccharide in PMA-primed THP-1 cells

Fei Chen, Douglas C. Kuhn, Lesley J. Gaydos, Laurence M. Demers

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Nitric oxide (NO), a nitrogen-free radical, plays an important role in mediating inflammatory reaction and cytotoxicity of tissue. To determine 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-1 cells, a monocyte-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-1 cells in vitro following the priming of these cells with the phorbol ester PMA. Both nitric oxide synthase inhibitor N-monomethyl-L-arginine (NMMA) and xanthine oxidase inhibitor allopurinol can partially suppress silica-induced NO production in PMA-primed THP-1 cells. Northern blot analysis indicated that, after 2 h of silica exposure, PMA-primed THP-1 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 attributed to its ability to initiate excessive production of nitric oxide from macrophages.

Original languageEnglish (US)
Pages (from-to)176-182
Number of pages7
JournalAPMIS
Volume104
Issue number3
StatePublished - Dec 1 1996

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Immunology and Allergy
  • Microbiology (medical)

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