Transforming growth factor-β1 inhibits interleukin-1β-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-1β and TGF-β1 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-β1, or 1 nmol/L IL-1β, or their combination in presence or absence of anti-TGF-β 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-β1 reversed IL-1β-induced expression of iNOS, CXCL6, IL1R1, MMP12, and CTSS, while upregulated TIMP2 expression. Furthermore, anti-TGF-β neutralizing antibody abrogated TGF-β effects. Combination with IL-1β and TGF-β1 induced the expression of IL1α, IL1β, IL1R1, and CTSS, but suppressed CST3 expression. CTSS expression in the combination treatment was higher than that of cells treated with anti-TGF-β antibodies alone. Moreover, IL-1β-induced CTSS enzymatic activity was reduced when human vSMCs were co-treated with TGF-β, whereas this reduction was abrogated by anti-TGF-β neutralizing antibody.

Conclusion: TGF-β1 abrogated IL-1β-induced expression of inflammatory genes and elastolytic activity in cultured human vSMCs. Thus, TGF-β1 can play a crucial role in impairing IL-1β-induced vascular inflammation and damage involved in the etiology of cardiovascular diseases.