Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner.
We have investigated the effect of interleukin 6 (IL-6) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortas. Murine recombinant IL-6 significantly increased the number of VSMC and stimulated tritiated thymidine incorporation into VSMC in a dose-dependent manner. The IL-6-induced thymidine incorporation into VSMC was totally inhibited by the Ca2+ channel blocker verapamil; however, IL-6 showed no effects on the intracellular Ca2+ level ([Ca2+]i) in VSMC. Antibody against platelet-derived growth factor (PDGF) also totally inhibited the IL-6-induced thymidine uptake. PDGF caused a significant increase in the [Ca2+]i, which was totally inhibited by verapamil. IL-6 mRNA was not detected in unstimulated "quiescent" VSMC, but its expression was stimulated by exposure of VSMC to 10% fetal bovine serum. Immunohistochemical study using anti-PDGF antibody showed that IL-6 stimulated PDGF production in VSMC. These results support the premise that IL-6 is released by VSMC in an autocrine manner and promotes the growth of VSMC via induction of endogenous PDGF production.
Ikeda
U
U
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ikeda
M
M
Oohara
T
T
Oguchi
A
A
Kamitani
T
T
Tsuruya
Y
Y
Kano
S
S
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D009994:Osmolar Concentration; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013194:Staining and Labeling
D000906:Antibodies; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D002118:Calcium