Modulation of murine dendritic cell function by adenine nucleotides and adenosine:: Involvement of the A2B receptor

被引:111
作者
Ben Addi, Abduelhakem [1 ]
Lefort, Anne [2 ]
Hua, Xiaoyang [3 ]
Libert, Frederick [2 ]
Communi, Didier [2 ]
Ledent, Catherine [2 ]
Macours, Pascale [4 ]
Tilley, Stephen L. [3 ]
Boeynaems, Jean-Marie [2 ,4 ]
Robaye, Bernard [1 ]
机构
[1] Univ Libre Bruxelles, IRIBHM, IBMM, Inst Interdisciplinary Res, B-6041 Gosselies, Belgium
[2] Univ Libre Bruxelles, IRIBHM, Inst Interdisciplinary Res, Brussels, Belgium
[3] Univ N Carolina, Dept Med, Div Pulm & Crit Care Med, Chapel Hill, NC USA
[4] Univ Libre Bruxelles, Erasme Hosp, Dept Med Chem, Brussels, Belgium
关键词
cytokines; dendritic cells; gene regulation;
D O I
10.1002/eji.200737781
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Adenosine triphosphate has previously been shown to induce semi-mature human monocyte-derived dendritic cells (DC). These are characterized by the up-regulation of co-stimulatory molecules, the inhibition of IL-12 and the up-regulation of some genes involved in immune tolerance, such as thrombospondin-1 and indoleamine 2,3-dioxygenase. The actions of adenosine triphosphate are mediated by the P2Y(11) receptor; since there is no functional P2Y(11) gene in the murine genome, we investigated the action of adenine nucleotides on murine DC. Adenosine 5'-(3-thiotriphosphate) and adenosine inhibited the production of IL-12p70 by bone marrow-derived DC (BMDC). These inhibitions were relieved by 8-p-sulfophenyltheophylline, an adenosine receptor antagonist. The use of selective ligands and A(2B)(-/-) BMDC indicated the involvement of the A(2B) receptor. A microarray experiment, confirmed by quantitative PCR, showed that, in presence of LPS, 5'-(N-ethylcarboxamido) adenosine (NECA, the most potent A(2B) receptor agonist) regulated the expression of several genes: arginase I and II, thrombospondin-1 and vascular endothelial growth factor were up-regulated whereas CCL2 and CCL12 were down-regulated. We further showed that NECA, in combination with LPS, increased the arginase I enzymatic activity. In conclusion, the described actions of adenine nucleotides on BMDC are mediated. by their degradation product, adenosine, acting on the A(2B) receptor, and will possibly lead to an impairment of Th1 response or tolerance.
引用
收藏
页码:1610 / 1620
页数:11
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