Attenuation of Experimental Atherosclerosis by Interleukin-19

作者：Ellison Stephen; Gabunia Khatuna; Kelemen Sheri E; England Ross N; Scalia Rosario; Richards James M; Orr Wayne; Traylor James G Jr; Rogers Thomas; Cornwell William; Berglund Lisa M; Goncalves Isabel; Gomez Maria F; Autieri Michael V^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2013, 33(10): 2316-2324.

DOI：10.1161/ATVBAHA.113.301521

• atherosclerosis
• chemokines
• interleukin-19
• macrophages

Objective Interleukin-19 (IL-19) is a putative Th2, anti-inflammatory interleukin. Its expression and potential role in atherogenesis are unknown. IL-19 is not detected in normal artery and is expressed to a greater degree in plaque from symptomatic versus asymptomatic patients, suggesting a compensatory counter-regulatory function. We tested whether IL-19 could reduce atherosclerosis in susceptible mice and identified plausible mechanisms. %26lt;br%26gt;Approach and Results LDLR-/- mice fed an atherogenic diet and injected with either 1.0 or 10.0 ng/g per day recombinant mouse IL-19 had significantly less plaque area in the aortic arch compared with controls (P%26lt;0.0001). Weight gain, cholesterol, and triglyceride levels were not significantly different. Gene expression in splenocytes from IL-19-treated mice demonstrated immune cell Th2 polarization, with decreased expression of T-bet, interferon-, interleukin-1, and interleukin-12 and increased expression of GATA3 and FoxP3 mRNA. A greater percentage of lymphocytes were Th2 polarized in IL-19-treated mice. Cellular characterization of plaque by immunohistochemistry demonstrated that IL-19-treated mice have significantly less macrophage infiltrate compared with controls (P%26lt;0.001). Intravital microscopy revealed significantly less leukocyte adhesion in wild-type mice injected with IL-19 and fed an atherogenic diet compared with controls. Treatment of cultured endothelial cells, vascular smooth muscle cells, and bone marrow-derived macrophages with IL-19 resulted in a significant decrease in chemokine mRNA and mRNA stability protein human antigen R. %26lt;br%26gt;Conclusions These data suggest that IL-19 is a potent inhibitor of experimental atherosclerosis, with diverse mechanisms including immune cell polarization, decrease in macrophage adhesion, and decrease in gene expression. This may identify IL-19 as a novel therapeutic to limit vascular inflammation.

• 出版日期2013-10