Transforming growth factor β1 induces IL-1 receptor antagonist production and gene expression in rat vascular smooth muscle cells Original Research Article

Atherosclerosis is an inflammatory-fibroproliferative process that may represent a possible milieu in which transforming growth factor-β (TGF-β) can be involved. Vascular smooth muscle cells (VSMC) may represent a source or a target of a large number of growth factors and proinflammatory cytokines, including interleukin-1 and its receptor antagonist (IL-1Ra). We tested the effect of TGF-β1 on IL-1Ra production and gene expression in rat VSMC cultures. We found a significant dose (3–30 ng/ml) and time-dependent (0–48 h) increase in IL-1Ra immunoactivity in the supernatant of conditioned medium and cell lysates. The maximal effect was observed with TGF-β at 30 ng/ml and after 24 h incubation time, respect to untreated cells (320±26 vs. 211±20 pg/ml; P<0.01). Furthermore, TGF-β1 induced an increased mRNA expression which began at 2 h and peaked at 18 h incubation time (about a 6-fold increase with respect to unstimulated cells). The effect of TGF-β1 on IL-1Ra production was completely inhibited by an anti-IL-1β antibody (10 μg/ml) (from 320±81 to 181±46 pg/ml). These experiments suggest that TGF-β1, potentially produced in the vascular wall during atherogenesis, may play a pathophysiological role in the autocrine control of IL-1 actions, via VSMC IL-1Ra production.