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iNOS gene upregulation is associated with the early proliferative response of human lung fibroblasts to cytokine stimulation
Author(s) -
Romanska Hanna M.,
Polak Julia M.,
Coleman Robert A.,
James Rowena S.,
Harmer Daniel W.,
Allen Jennifer C.,
Bishop Anne E.
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1116
Subject(s) - downregulation and upregulation , nitric oxide synthase , stimulation , nitric oxide , fibroblast , pulmonary fibrosis , fibrosis , pathogenesis , lung , biology , cytokine , gene expression , immunology , pathology , endocrinology , medicine , gene , in vitro , biochemistry
Increased release of oxidants has been implicated in the pathogenesis of pulmonary fibrosis. Previous work in the rat showed that formation of the early fibrotic lesion is associated with increased expression of inducible nitric oxide synthase (iNOS) in pulmonary fibroblasts. The aim of this study was to test the hypothesis that NO is involved in the activation of pulmonary fibroblasts. The effects of endogenous and exogenous NO on proliferation of human pulmonary fibroblasts were investigated by administration of cytomix or SNAP, respectively. At low concentrations, both treatments increased cell numbers, an effect attenuated by iNOS inhibitor or NO scavenger. Induction of iNOS was confirmed by measurement of nitrate/nitrite production and by immunodetection. Quantitative RT‐PCR showed an increase in iNOS mRNA as early as 3 h after stimulation. These results support the hypothesis and show that upregulation of the iNOS gene is an early event in the proliferative response of human lung fibroblasts to inflammatory stimuli. Copyright © 2002 John Wiley & Sons, Ltd.