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- Title
IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis.
- Authors
McCarthy, Cathal; Duffy, Michelle M.; Mooney, Declan; James, William G.; Griffin, Matthew D.; Fitzgerald, Desmond J.; Belton, Orina
- Abstract
Conjugated linoleic acid (CLA) induces regression of preestablished atherosclerosis in the ApoE-/- mouse. Understanding the mechanisms involved may help in identifying novel pathways associated with the regression of human disease. Animals were administered a 1% cholesterol diet for 12 wk, with 1% CLA supplementation from wk 8 to 12. ApoE-/- mice fed only the 1% cholesterol diet for 12 wk were employed as controls. Transcriptomic analysis of mouse aorta showed that many of the components of the IL-10 signaling pathway were modified during CLA-induced regression. Real-time PCR and Western blot analysis showed increased IL-10 receptor expression, phosphorylation of STAT3, and downstream target gene expression in the aorta, alongside an increase in serum IL-10 (79.8±22.4 vs. 41.9+5.5 pg/ml, n=10; P<0.01). CLA -supplementation also increased IL-10 production in bone marrow-derived macrophages (143.6±28.6 vs. 94±5.6 pg/ml, n=5; P<0.05). To explore the mechanisms for altered EL-10 production, we examined the profile of monocyte/macrophage pheno-type in the vessel wall, bone marrow, and spleen. CLA increased macrophage polarization toward an anti-inflammatory M2 phenotype in vivo, increasing the population of Ly6Clo monocytes (29 vs. 77±14, n=5, P < 0.05) in the aorta. CLA had similar effects on monocytes/macrophages differentiated from marrow-derived progenitor cells and on splenocytes. The induction of IL-10 on CLA supplementation in this model may reflect a systemic alteration toward an anti-inflammatory phenotype, which, in turn promotes increased vascular infiltration by Ly6Clo monocytes. These cells may contribute to CLA-induced disease regression.
- Subjects
INTERLEUKIN-10; IMMUNOREGULATION; MACROPHAGES; MONOCYTES; ANTI-inflammatory agents; ATHEROSCLEROSIS
- Publication
FASEB Journal, 2013, Vol 27, Issue 2, p499
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.12-215442