DIFFERENTIAL-EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON THE EXPRESSION OF FIBRONECTIN AND COLLAGEN GENES IN CULTURED BOVINE ENDOTHELIAL-CELLS

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) (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 1(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.