Differential effects of tumor necrosis factor-alpha on the expression of fibronectin and collagen genes in cultured bovine endothelial cells.

Abstract

The effects of recombinant human tumor necrosis factor-alpha (TNF-alpha) on the expression of fibronectin and types (IV), (III), and (I) procollagen genes in cultured bovine pulmonary artery endothelial cells were examined in this study. Findings indicate that TNF-alpha increases steady-state levels of alpha l (IV) and alpha l (III) procollagen mRNAs while it decreases levels of fibronectin and alpha 2 (1) procollagen mRNA and leaves cytoskeletal actin mRNA levels unchanged. Both dose and exposure time moderated these effects. Treatment with TNF-alpha increased the stability of alpha l (IV) procollagen mRNA. The half-life of this mRNA, previously unreported in the literature, was increased by 118%, while the stability of fibronectin mRNA decreased by 44%. The stability of mRNAs for procollagens alpha l (III) and alpha 2 (I) were unchanged. Except in the case of procollagen alpha l (III), these effects were blocked by cycloheximide. Protein production induced by TNF-alpha was evaluated by immunoprecipitating proteins from the media and cell lysates. Our data indicate that TNF-alpha has a strong pretranslational regulatory role in cultured endothelial cell's expression of extracellular matrix protein genes.