Effects of Tumor Necrosis Factor-α on the Synthesis of DNA, the Secretion of Matrix Metalloproteinases/Tissue Inhibitors of Metalloproteinases, and the Activity of Invasive Migration in Cultured Vascular Smooth Muscle Cells

Abstract

To address the question of whether or not tumor necrosis factor-α (TNF-α) regulates the functions of vascular smooth muscle cells (SMCs), dense or sparse cultures of the cells derived from human aorta were treated with TNF-α or TNF-αneutralizing antibody (TNF-α Ab). The incorporation of [³H]thymidine into the acid-insoluble fraction of SMCs was significantly inhibited by TNF-α, but stimulated by TNF-α Ab only when the cells had a high cell density. TNF-αsignificantly increased the accumulation of matrix metalloproteinase-1 and -3 (MMT-1 and -3, respectively) in the conditioned medium of dense SMCs, but does not affect that of tissue inhibitors of metalloproteinases-1 (TIMP-1); MMP-9 and TIMP-2 were undetectable. The invasive migration of SMCs determined by a Transwell system was stimulated by neither TNF-α nor TNF-α Ab. Taking these results together, it is suggested that TNF-α regulates DNA and MMP synthesis in dense SMCs but does not affect their invasive migration.