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Fibroblast tropoelastin and alpha-smooth-muscle actin expression are repressed by particulate-activated macrophage-derived tumor necrosis factor-alpha in experimental silicosis.

Abstract：

:Lung elastin synthesis is normally confined to periods of development, is maximal during alveolarization, and declines to low levels in mature lung. We have previously described an elastogenic response in the adult rat lung associated with experimental granulomatous disease induced by silica instillation. Reinitiated tropoelastin expression was identified throughout the lung in fibroblasts expressing alpha-smooth-muscle actin, whereas fibroblasts within the granulomatous lesions failed to express both tropoelastin and alpha-smooth- muscle actin (Mariani and colleagues, Am. J. Pathol. 1995;147:988-1000). We hypothesized that inflammatory cells within the granulomatous lesions produce factors that alter fibroblast phenotype. We found that macrophages accumulating within granulomatous lesions of silicotic rat lungs produce and secrete tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine previously appreciated as a repressor of tropoelastin gene expression. In experimental cell systems, macrophages activated by particulates, either in vivo or in vitro, conditioned medium with a tropoelastin-repressing activity. This activity repressed both tropoelastin and alpha-smooth-muscle actin expression in primary cultures of rat lung fibroblasts in a time- dependent, transient manner. The particulate-activated macrophage-conditioned medium was found to contain TNF-alpha, which was both necessary and sufficient to induce these changes in lung fibroblast gene expression. These data indicate that macrophage-derived factors can modulate lung fibroblast tropoelastin expression in the diseased lung. Furthermore, the findings extend the association between expression by lung fibroblasts of tropoelastin and alpha-smooth-muscle actin.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Mariani TJ,Arikan MC,Pierce RA

doi

10.1165/ajrcmb.21.2.3641

keywords:

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

185-92

issue

eissn

1044-1549

issn

1535-4989

journal_volume

pub_type

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Fibroblast tropoelastin and alpha-smooth-muscle actin expression are repressed by particulate-activated macrophage-derived tumor necrosis factor-alpha in experimental silicosis.