Cytokine and pharmacological regulation of lung fibroblast proliferation.
Reist-RH; Blackford-J; Vrana-K; Castranova-V; Dey-R
Toxicologist 1992 Feb; 12(1):390
Our objective was to study the role of macrophage-derived cytokines in fibroblast proliferation. [3H] thymdine incorporation was shown to correlate well with fibroblast proliferation. In vitro treatment of alveolar macrophages with silica (150microg/ml) resulted in the production of an agent(s) which inhibits fibroblast proliferation. Indomethacin, a prostaglandin synthetase inhibitor, reversed this inhibition and unmasked a previously unseen competence factor(s). Further, the proliferative action of exogenous PDGF was reduced when fibroblasts were treated with supernate from silica-exposed macrophages, presumably due to the inhibitory action of prostaglandins. Silica-induced pulmonary fibrosis may result from decreased release of prostaglandins and/or increased release of proliferative factors from alveolar macrophages. Indeed, macrophages harvested 40 days after intratracheal instillation of silica (42mg/rat) produced an agent(s) which significantly stimulated [3H] thymidine incorporation by pulmonary fibroblasts. The antifibrotic drug, tetrandrine, inhibited [3H] thymidine incorporation and fibroblast proliferation in response to either serum or PDGF plus plasma. Thus, tetrandrine may be a useful probe to study fibrogenesis. (BOM-5431)
Lung-function; Lung-disorders; Lung-disease; Lung-tissue; Cell-function; Cellular-function; Pulmonary-system; Pulmonary-function; Pulmonary-system-disorders; Respiratory-system-disorders; Fibrosis
The Toxicologist. Society of Toxicology 31st Annual Meeting, February 23-27,1992, Seattle, Washingtion