title: Losartan attenuates human monocyte-derived dendritic cell immune maturation via downregulation of lectin-like oxidized low-density lipoprotein receptor-1.
abstract: The angiotensin II receptor-1 blockers have generally been shown to have antiatherogenic effects, and dendritic cells (DCs) are the most efficient antigen presenting cells that play an active role in the development of atherosclerosis through inflammatory-immune responses. Here, we tested the hypothesis that the antiatherogenic effect of losartan, the first angiotensin II receptor-1 blockers, might partly be mediated by attenuating DCs maturation. In this study, we showed that oxidized low-density lipoprotein (oxLDL) and angiotensin II (Ang II) could induce the maturation of human monocyte-derived DCs, stimulate CD83, HLA-DR expressions and IL-12, interferon-gamma secretions and increase the capacity of DCs to stimulate T-cell proliferation, which were suppressed by losartan. OxLDL could promote the autocrine secretion of Ang II by DCs and upregulate the expressions of 3 scavenger receptors SR-A, CD36, and LOX-1. Losartan reduced oxLDL-induced LOX-1 expression but not SR-A and CD36 expressions. Ang II could only upregulate the LOX-1 expression, which was reduced by losartan. OxLDL- and Ang II-induced upregulation of CD83 and secretion of IL-12 were all attenuated by LOX-1 neutralizing antibody. In conclusion, losartan could attenuate the oxLDL- and Ang II-induced immune maturation of human monocyte-derived DCs partly through downregulation of the LOX-1 expression.
authors.affiliation: Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Huang
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
authors.forename: Hongying
authors.initials: H
authors.lastname: Liu
authors.forename: Kang
authors.initials: K
authors.lastname: Yao
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D018955:CD36 Antigens / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000187:drug effects* / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D015703:Antigens, CD; D018955:CD36 Antigens; D002352:Carrier Proteins; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D018664:Interleukin-12; D008077:Lipoproteins, LDL; D019808:Losartan; D008562:Membrane Glycoproteins; D051127:Scavenger Receptors, Class E; D000068103:Serine-Arginine Splicing Factors; D000097802:CD83 Antigen; C495137:OLR1 protein, human; C503566:SCAF1 protein, human; C099252:oxidized low density lipoprotein