Losartan attenuates human monocyte-derived dendritic cells immune maturation via downregulation of lectin-like oxidized low density lipoprotein receptor-1
Journal of Cardiovascular Pharmacology, 05/16/2012Huang D et al.
Losartan could attenuate the oxLDL– and Ang II–induced immune maturation of human monocyte–derived DCs partly through downregulation of the LOX–1 expression.
The angiotensin II receptor 1 blockers (ARBs) have generally been shown to have anti–atherogenic 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, authors tested the hypothesis that the anti–atherogenic effect of losartan, the first ARB, might partly be mediated by attenuating DCs maturation.
In this study authors 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, IFN–[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 three 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.
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