PPARγ activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties
PPARγ activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties
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DOI：
10.1016/j.cmet.2007.06.010
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发表时间：
2007-08-01
期刊：
影响因子：
29
通讯作者：
Chinetti-Gbaguidi, Giulia
中科院分区：
文献类型：
--
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
Th1细胞因子促进单核细胞分化为促动脉粥样硬化的M1巨噬细胞，而Th2细胞因子导致一种“替代性”抗炎的M2巨噬细胞表型。在此我们表明，在人类动脉粥样硬化病变中，M2标志物的表达与过氧化物酶体增殖物激活受体γ（一种控制巨噬细胞炎症的核受体）呈正相关。此外，过氧化物酶体增殖物激活受体γ的激活促使原代人类单核细胞向M2分化，从而使M1巨噬细胞具有更显著的抗炎活性。然而，过氧化物酶体增殖物激活受体γ的激活并不影响静息或M1巨噬细胞中M2标志物的表达，过氧化物酶体增殖物激活受体γ激动剂治疗也不影响动脉粥样硬化病变中M2标志物的表达，这表明只有天然单核细胞可通过过氧化物酶体增殖物激活受体γ的激活而被诱导为增强的M2表型。此外，过氧化物酶体增殖物激活受体γ的激活显著增加循环外周血单核细胞中M2标志物MR的表达。这些数据表明过氧化物酶体增殖物激活受体γ的激活使人类单核细胞偏向抗炎的M2表型。
Th1 cytokines promote monocyte differentiation into proatherogenic M1 macrophages, while Th2 cytokines lead to an "alternative" anti-inflammatory M2 macrophage phenotype. Here we show that in human atherosclerotic lesions, the expression of M2 markers and PPAR gamma, a nuclear receptor controlling macrophage inflammation, correlate positively. Moreover, PPAR gamma activation primes primary human monocytes into M2 differentiation, resulting in a more pronounced anti-inflammatory activity in M1 macrophages. However, PPAR gamma activation does not influence M2 marker expression in resting or M1 macrophages, nor does PPAR gamma agonist treatment influence the expression of M2 markers in atherosclerotic lesions, indicating that only native monocytes can be primed by PPAR gamma activation to an enhanced M2 phenotype. Furthermore, PPAR gamma activation significantly increases expression of the M2 marker MR in circulating peripheral blood mononuclear cells. These data demonstrate that PPAR gamma activation skews human monocytes toward an anti-inflammatory M2 phenotype.