IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation

Stephen Ellison, Khatuna Gabunia, James M. Richards, Sheri E. Kelemen, Ross N. England, Dan Rudic, Yasu Taka Azuma, M. Alexandra Munroy, Satoru Eguchi, Michael V. Autieri

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

We tested the hypothesis that IL-19, a putative member of the type 2 helper T-cell family of anti-inflammatory interleukins, can attenuate intimal hyperplasia and modulate the vascular smooth muscle cell (VSMC) response to injury. Ligated carotid artery of IL-19 knockout (KO) mice demonstrated a significantly higher neointima/intima ratio compared with wild-type (WT) mice (P = 0.04). More important, the increased neointima/intima ratio in the KO could be reversed by injection of 10 ng/g per day recombinant IL-19 into the KO mouse (P = 0.04). VSMCs explanted from IL-19 KO mice proliferated significantly more rapidly than WT. This could be inhibited by addition of IL-19 to KO VSMCs (P = 0.04 and P < 0.01). IL-19 KO VSMCs migrated more rapidly compared with WT (P < 0.01). Interestingly, there was no type 1 helper T-cell polarization in the KO mouse, but there was significantly greater leukocyte infiltrate in the ligated artery in these mice compared with WT. IL-19 KO VSMCs expressed significantly greater levels of inflammatory mRNA, including IL-1β, tumor necrosis factor α, and monocyte chemoattractant protein-1 in response to tumor necrosis factor α stimulation (P < 0.01 for all). KO VSMCs expressed greater adhesion molecule expression and adherence to monocytes. Together, these data indicate that IL-19 is a previously unrecognized counterregulatory factor for VSMCs, and its expression is an important protective mechanism in regulation of vascular restenosis.

Original languageEnglish (US)
Pages (from-to)2134-2143
Number of pages10
JournalAmerican Journal of Pathology
Volume184
Issue number7
DOIs
StatePublished - Jul 2014

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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