Modulation of collagen synthesis by tumor necrosis factor alpha in cultured vascular smooth muscle cells

Collagen synthesis in vascular smooth muscle cells (SMCs) after exposure to tumor necrosis factor alpha (TNF-alpha) was investigated using a culture s ystem. The synthesis of collagenase-digestible proteins (CDP) and noncollag enous proteins (NCP) was evaluated by the [H-3]proline incorporation. It wa s shown that TNF-alpha markedly suppresses the incorporation of [H-3]prolin e into both CDP and NCP in confluent cultures of SMCs but not in sparse cul tures of the cells. Such a marked suppression by TNF-alpha was not observed in confluent bovine aortic endothelial cells and human fibroblastic IMR-90 cells. In confluent SMCs, the synthesis of CDP was more strongly inhibited by TNF-alpha than that of NCP. When the CDP synthesis was stimulated by tr ansforming growth factor beta, TNF-alpha suppressed the stimulation in both confluent and sparse SMCs. Human SMCs synthesized types I, III, IV and V c ollagens; TNF-alpha markedly decreased the relative proportion of types IV and V. It was therefore suggested that TNF-alpha modulates the collagen syn thesis by SMCs depending on their cell density and modifies the formation o f atherosclerotic lesions.