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

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