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, Radu Daniel Rudic, Yasu Taka Azuma, M. Alexandra Munroy, Satoru Eguchi, Michael V. Autieri

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 - Jan 1 2014

Fingerprint

Vascular Smooth Muscle
Knockout Mice
Smooth Muscle Myocytes
Hyperplasia
Ligation
Neointima
Tumor Necrosis Factor-alpha
Tunica Intima
Th2 Cells
Th1 Cells
Chemokine CCL2
Interleukins
Interleukin-1
Carotid Arteries
Blood Vessels
Monocytes
Leukocytes
Anti-Inflammatory Agents
Arteries
Messenger RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation. / Ellison, Stephen; Gabunia, Khatuna; Richards, James M.; Kelemen, Sheri E.; England, Ross N.; Rudic, Radu Daniel; Azuma, Yasu Taka; Munroy, M. Alexandra; Eguchi, Satoru; Autieri, Michael V.

In: American Journal of Pathology, Vol. 184, No. 7, 01.01.2014, p. 2134-2143.

Research output: Contribution to journalArticle

Ellison, S, Gabunia, K, Richards, JM, Kelemen, SE, England, RN, Rudic, RD, Azuma, YT, Munroy, MA, Eguchi, S & Autieri, MV 2014, 'IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation', American Journal of Pathology, vol. 184, no. 7, pp. 2134-2143. https://doi.org/10.1016/j.ajpath.2014.04.001
Ellison, Stephen ; Gabunia, Khatuna ; Richards, James M. ; Kelemen, Sheri E. ; England, Ross N. ; Rudic, Radu Daniel ; Azuma, Yasu Taka ; Munroy, M. Alexandra ; Eguchi, Satoru ; Autieri, Michael V. / IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation. In: American Journal of Pathology. 2014 ; Vol. 184, No. 7. pp. 2134-2143.
@article{598e3fed1d214d488a73ed9ef3dc6765,
title = "IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation",
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.",
author = "Stephen Ellison and Khatuna Gabunia and Richards, {James M.} and Kelemen, {Sheri E.} and England, {Ross N.} and Rudic, {Radu Daniel} and Azuma, {Yasu Taka} and Munroy, {M. Alexandra} and Satoru Eguchi and Autieri, {Michael V.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.ajpath.2014.04.001",
language = "English (US)",
volume = "184",
pages = "2134--2143",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation

AU - Ellison, Stephen

AU - Gabunia, Khatuna

AU - Richards, James M.

AU - Kelemen, Sheri E.

AU - England, Ross N.

AU - Rudic, Radu Daniel

AU - Azuma, Yasu Taka

AU - Munroy, M. Alexandra

AU - Eguchi, Satoru

AU - Autieri, Michael V.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84903179617&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903179617&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2014.04.001

DO - 10.1016/j.ajpath.2014.04.001

M3 - Article

C2 - 24814101

AN - SCOPUS:84903179617

VL - 184

SP - 2134

EP - 2143

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 7

ER -