IL-10 inhibits vascular smooth muscle cell activation in vitro and in vivo.

  • Mazighi M
  • Pelle A
  • Gonzalez W
 et al. 
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Abstract

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.

Author-supplied keywords

  • Animals
  • Aorta
  • Catheterization
  • Cell Division
  • Cell Movement
  • Cells, Cultured
  • Gene Expression
  • Hyperplasia
  • I-kappa B Proteins
  • Interleukin-10
  • Interleukin-6
  • Male
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • NF-kappa B
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Recombinant Proteins
  • Tunica Intima
  • Wounds and Injuries
  • adverse effects
  • cytology
  • drug effects
  • etiology
  • genetics
  • injuries
  • metabolism
  • pathology
  • pharmacology
  • physiology
  • physiopathology

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Authors

  • Mikael Mazighi

  • Anne Pelle

  • Walter Gonzalez

  • El Mostafa Mtairag

  • Monique Philippe

  • Dominique Henin

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