IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis.
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 IL-10 production, we examined the profile of monocyte/macrophage phenotype in the vessel wall, bone marrow, and spleen. CLA increased macrophage polarization toward an anti-inflammatory M2 phenotype in vivo, increasing the population of Ly6C(lo) 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 Ly6C(lo) monocytes. These cells may contribute to CLA-induced disease regression.
School of Biomedical and Biomolecular Sciences, University College Dublin Conway Institute, University College Dublin, Dublin, Ireland.
Cathal
C
McCarthy
Michelle M
MM
Duffy
Declan
D
Mooney
William G
WG
James
Matthew D
MD
Griffin
Desmond J
DJ
Fitzgerald
Orina
O
Belton
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D001057:Apolipoproteins E; C556062:IL10 protein, mouse; D044243:Linoleic Acids, Conjugated; D016753:Interleukin-10