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.
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ellison
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Khatuna
authors.initials: K
authors.lastname: Gabunia
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: James M
authors.initials: JM
authors.lastname: Richards
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Sheri E
authors.initials: SE
authors.lastname: Kelemen
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ross N
authors.initials: RN
authors.lastname: England
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, Georgia.
authors.forename: Dan
authors.initials: D
authors.lastname: Rudic
authors.affiliation: Laboratory of Veterinary Pharmacology, Osaka Prefecture University Graduate School, Osaka, Japan.
authors.forename: Yasu-Taka
authors.initials: YT
authors.lastname: Azuma
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: M Alexandra
authors.initials: MA
authors.lastname: Munroy
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
authors.affiliation: Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania. Electronic address: mautieri@temple.edu.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Autieri
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006965:Hyperplasia / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism*; D007378:Interleukins; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D058426:Neointima / Q000473:pathology*; D011994:Recombinant Proteins / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology
chemical_list: C498891:Il19 protein, mouse; D007378:Interleukins; D011994:Recombinant Proteins; D016753:Interleukin-10