IL-10 inhibits vascular smooth muscle cell activation in vitro and in vivo.
The anti-inflammatory cytokine IL-10 inhibits intimal hyperplasia after stent implantation via a powerful inactivation of monocytes. We tested the hypothesis that IL-10 may also inhibit vascular smooth muscle cell (SMC) activation via the inhibition of the NF-kappaB/I-kappaB system. The IL-10 receptor was detected in rat SMCs in vitro and in vivo. In LPS-stimulated rat SMCs, 1 ng/ml recombinant murine IL-10 (mIL-10) reduced I-kappaBalpha and I-kappaBbeta degradation, NF-kappaB activation, as well as the expression of the NF-kappaB-dependent gene IL-6 by 32%, 31%, 75%, and 19%, respectively (P < 0.05 for all). Similar results were obtained in vivo 6 h and 4 days after balloon abrasion of the rat aorta, a model in which intimal hyperplasia results essentially from SMC activation. Moreover, mIL-10 reduced SMC proliferation and migration in vitro (by 60% for both, P < 0.0001), resulting in reduced SMC proliferation and intimal growth 14 days after balloon abrasion of the rat aorta (by 76% and 75%, respectively; P < 0.005). In conclusion, mIL-10 has a direct inhibitory effect on SMCs in vitro and in vivo. This effect is mediated in part by NF-kappaB inactivation and may participate in the overall protective effect of IL-10 on postangioplasty restenosis.
Mazighi
Mikael
M
U460 Institut National de la Santé et de la Recherche Médicale, 5018 Paris, France.
Pellé
Anne
A
Gonzalez
Walter
W
Mtairag
El Mostafa
el M
Philippe
Monique
M
Hénin
Dominique
D
Michel
Jean-Baptiste
JB
Feldman
Laurent J
LJ
D000818:Animals; D001011:Aorta / Q000293:injuries / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006965:Hyperplasia; D020672:I-kappa B Proteins / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins / Q000494:pharmacology; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014947:Wounds and Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D016753:Interleukin-10