Arteriosclerosis, thrombosis, and vascular biology, 2013-10, Vol.33 (10), p.2316-2324
2013
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- Autor(en) / Beteiligte
- Titel
- Attenuation of experimental atherosclerosis by interleukin-19
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2013-10, Vol.33 (10), p.2316-2324
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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<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-γ, interleukin-1β, and interleukin-12β 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<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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1079-5642eISSN: 1524-4636DOI: 10.1161/atvbaha.113.301521Titel-ID: cdi_pubmed_primary_23950143
- Format
- –
- Schlagworte
- Aged, Animals, Aorta - drug effects, Aorta - immunology, Aorta - metabolism, Aorta - pathology, Aortic Diseases - genetics, Aortic Diseases - immunology, Aortic Diseases - metabolism, Aortic Diseases - pathology, Aortic Diseases - prevention & control, Apolipoproteins E - deficiency, Apolipoproteins E - genetics, Atherosclerosis - genetics, Atherosclerosis - immunology, Atherosclerosis - metabolism, Atherosclerosis - pathology, Atherosclerosis - prevention & control, Biomarkers - blood, Carotid Artery Diseases - immunology, Carotid Artery Diseases - pathology, Cells, Cultured, Cholesterol - blood, Disease Models, Animal, Endothelial Cells - drug effects, Endothelial Cells - immunology, Female, Gene Expression Regulation - drug effects, Humans, Inflammation Mediators - metabolism, Interleukin-10 - metabolism, Interleukin-10 - pharmacology, Interleukins - metabolism, Macrophages - drug effects, Macrophages - immunology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Myocytes, Smooth Muscle - drug effects, Myocytes, Smooth Muscle - immunology, Plaque, Atherosclerotic, Receptors, LDL - deficiency, Receptors, LDL - genetics, Recombinant Proteins - pharmacology, Spleen - drug effects, Spleen - immunology, Th2 Cells - drug effects, Th2 Cells - immunology, Time Factors, Triglycerides - blood