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IL‐19 Attenuates Progression of Atherosclerosis, Modifies Macrophage Phenotype and Lipid Uptake in Macrophage and VSMC
Author(s) -
Gabunia Khatuna,
Ellison Stephen,
Kelemen Sheri,
Richards James,
Autieri Michael
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.869.6
Subject(s) - macrophage , vascular smooth muscle , flow cytometry , foam cell , phenotype , recombinant dna , chemistry , inflammation , ldl receptor , endocrinology , m2 macrophage , medicine , microbiology and biotechnology , biology , lipoprotein , immunology , biochemistry , cholesterol , in vitro , smooth muscle , gene
We tested the hypothesis that administration of exogenous IL‐19 could attenuate development of pre‐formed atherosclerotic plaque, and attempted to identify potential molecular mechanisms. LDLR−/− mice were fed a high‐fat diet for 14 weeks, then administered 10ng/g/day IL‐19 or PBS for an additional 8 weeks. En face analysis demonstrated that IL‐19 could significantly inhibit accumulation of additional plaque in these mice. To determine potential mechanisms, bone marrow derived macrophages (BMDM) from IL‐19−/− mice had significantly less ox LDL uptake compared to wild‐type BMDM as determined by flow cytometry. Addition of recombinant IL‐19 to wild type BMDM increased lipid uptake and expression of lipid efflux proteins. Vascular smooth muscle cells (VSMC) also form foam cells, and VSMC isolated from IL‐19−/− mice had increased uptake of ox LDL, and addition of recombinant IL‐19 to human VSMC reduced their uptake of ox LDL. BMDM from IL‐19 treated LDLR−/− mice demonstrated a shift to the M2 alternatively activated macrophage, with decreased IL‐12, and increased YM1 mRNA expression. These data demonstrate for the first time that IL‐19 can inhibit progression of existing atherosclerotic plaque, modulate lipid uptake in smooth muscle and macrophage, and polarize macrophage to the M2 phenotype.