TRANSFORMING-GROWTH-FACTOR BETA(1), INDUCES IL-1 RECEPTOR ANTAGONIST PRODUCTION AND GENE-EXPRESSION IN RAT VASCULAR SMOOTH-MUSCLE CELLS

Atherosclerosis is an inflammatory-fibroproliferative process that may represent a possible milieu in which transforming growth factor-beta (TGF-beta) can be involved. Vascular smooth muscle cells (VSMC) may re present a source or a target of a large number of growth factors and p roinflammatory cytokines, including interleukin-1 and its receptor ant agonist (IL-1Ra). We tested the effect of TGF-beta(1) on IL-1Ra produc tion 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 immun oactivity in the supernatant of conditioned medium and cell lysates. T he maximal effect was observed with TGF-beta 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-beta(1) induced an increased mRN A expression which began at 2 h and peaked at 18 h incubation time (ab out a 6-fold increase with respect to unstimulated cells). The effect of TGF-beta(1) on IL-1Ra production was completely inhibited by an ant i-IL-1 beta antibody (10 mu g/ml) (from 320 +/- 81 to 181 +/- 46 pg/ml ). These experiments suggest that TGF-beta(1), 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 produc tion. (C) 1998 Elsevier Science Ireland Ltd.