Oxidized low-density lipoprotein-induced proinflammatory cytokine response in macrophages are suppressed by CD4CD25(+)Foxp3(+) regulatory T cells through downregulating toll like receptor 2-mediated activation of NF-kappaB.
CD4(+)CD25(+) regulatory T cells (Tregs) exert a suppressive activity on atherosclerosis but the underlying mechanism remains unclear. Here, we investigated whether and how Tregs affect oxLDL-induced proinflammatory response in macrophages. Tregs were isolated by magnetic cell sorting-column and analyzed by flow cytometry. Macrophages were cultured with or without Tregs in the presence of oxLDL for 48 hours to induce proinflammatory response. Our data showed that with oxLDL challenge, the Treg-modulated macrophages have decreased NO production and iNOS expression, decreased HLA-DR and CD86 expression, and down-regulated proinflammatory cytokine/chemokine production. Tregs can inhibit the pro-inflammatory properties of macrophages and steer macrophage differentiation toward an anti-inflammatory cytokine producing phenotype. Mechanistic studies reveal that Treg-mediated suppression of the monocyte response to oxLDL was reflected by a reduction in the up-regulation of NF-kappaB activity accompanied by a decreased expression of TLR2 but not TLR4 at the transcriptional level. These results suggest that CD4(+)CD25(+)Foxp3(+) regulatory T cells may exert its suppressive functions on pro-inflammatory properties of OxLDL induced-macrophages partly through TLR2-NF-kappaB signaling pathway.
Department of Cardiology, Institute of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Ming
M
Li
Jing
J
Lin
Zhixiao
Z
Wang
Shaolin
S
He
Xuming
X
Ma
Dazhu
D
Li
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005786:Gene Expression Regulation; D008077:Lipoproteins, LDL / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D009589:Nitrogen Oxides / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D009589:Nitrogen Oxides; D051195:Toll-Like Receptor 2; C099252:oxidized low density lipoprotein; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse