Transforming growth factor-beta 1 inhibits interleukin-1 beta-induced expression of inflammatory genes and Cathepsin S activity in human vascular smooth muscle cells

Objective and design This study investigated the opposite mechanisms by which IL-1 beta and TGF-beta 1 modulated the inflammatory and migratory phenotypes in cultured human intimal vascular smooth muscle cells vSMCs. Materials and treatment Primary human vSMCs, obtained from twelve hypertensive patients who underwent carotid endarterectomy, were incubated for 24 hours with either 40 pM TGF-beta 1, or 1 nmol/L IL-1 beta, or their combination in presence or absence of anti-TGF-beta neutralizing antibody. Methods The expression levels of matrix metalloproteases and their inhibitors, and the elastolytic enzyme cathepsin S (CTSS) and its inhibitor cystatin C were evaluated with RT-PCR. CTSS activity was measured by fluorometry. Results TGF-beta 1 reversed IL-1 beta-induced expression of iNOS, CXCL6, IL1R1, MMP12, and CTSS, while upregulated TIMP2 expression. Furthermore, anti-TGF-beta neutralizing antibody abrogated TGF-beta effects. Combination with IL-1 beta and TGF-beta 1 induced the expression of IL1 alpha, IL1 beta, IL1R1, and CTSS, but suppressed CST3 expression. CTSS expression in the combination treatment was higher than that of cells treated with anti-TGF-beta antibodies alone. Moreover, IL-1 beta-induced CTSS enzymatic activity was reduced when human vSMCs were co-treated with TGF-beta, whereas this reduction was abrogated by anti-TGF-beta neutralizing antibody. Conclusion TGF-beta 1 abrogated IL-1 beta-induced expression of inflammatory genes and elastolytic activity in cultured human vSMCs. Thus, TGF-beta 1 can play a crucial role in impairing IL-1 beta-induced vascular inflammation and damage involved in the etiology of cardiovascular diseases.