Transforming growth factor beta1 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 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-beta1, 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-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-beta1 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-beta1 on IL-1Ra production was completely inhibited by an anti-IL-1beta antibody (10 microg/ml) (from 320 +/- 81 to 181 +/- 46 pg/ml). These experiments suggest that TGF-beta1, 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.
Di Febbo
C
C
Department of Medicine and Science of Ageing, University of Chieti Medical School, Italy.
Baccante
G
G
Reale
M
M
Castellani
M L
ML
Angelini
A
A
Cuccurullo
F
F
Porreca
E
E
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D002478:Cells, Cultured; D015870:Gene Expression; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology
D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta