PPAR activation induces M1 macrophage polarization via cPLA₂-COX-2 inhibition, activating ROS production against Leishmania mexicana.
PPAR activation induces M1 macrophage polarization via cPLA₂-COX-2 inhibition, activating ROS production against Leishmania mexicana.
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DOI：
10.1155/2013/215283
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发表时间：
2013
影响因子：
--
通讯作者：
Talamás-Rohana P
中科院分区：
文献类型：
--
作者：
Díaz-Gandarilla JA;Osorio-Trujillo C;Hernández-Ramírez VI;Talamás-Rohana P
对利什曼原虫的防御依赖于Th 1炎症反应，并且在易感模型中的主要问题是巨噬细胞的杀利什曼原虫活性随着IL-10、IL-4和考克斯-2上调以及免疫抑制性PGE 2的关闭，所有这些一起抑制呼吸爆发。过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）的激活是负责巨噬细胞极化利什曼原虫易感模型，其中杀微生物剂的功能被灭活。本文证明了，至少对L.在墨西哥黑曲霉中，以过氧化物酶体增殖物激活体（主要是过氧化物酶体增殖物激活体γ）激活巨噬细胞，使巨噬细胞向M1方向极化，并增强其对胞内病原菌L.墨西哥。PPAR激活诱导IL-10下调，而促炎细胞因子如TNF-α、IL-1β和IL-6的产生仍然很高。此外，PPAR激动剂处理诱导cPLA 2-考克斯-2-胡萝卜素途径的失活以及TLR 4表达的增加，所有这些标准均符合M1巨噬细胞特征。最后，寄生虫的负担，在治疗的巨噬细胞，低于感染的未治疗的巨噬细胞，最有可能与这些治疗的细胞呼吸爆发的增加。基于上述数据，我们得出结论，这项工作中使用的PPAR激动剂诱导M1巨噬细胞极化通过抑制cPLA 2和增加积极的杀微生物活性通过活性氧（ROS）的生产。
Defence against Leishmania depends upon Th1 inflammatory response and, a major problem in susceptible models, is the turnoff of the leishmanicidal activity of macrophages with IL-10, IL-4, and COX-2 upregulation, as well as immunosuppressive PGE2, all together inhibiting the respiratory burst. Peroxisome proliferator-activated receptors (PPAR) activation is responsible for macrophages polarization on Leishmania susceptible models where microbicide functions are deactivated. In this paper, we demonstrated that, at least for L. mexicana, PPAR activation, mainly PPARγ, induced macrophage activation through their polarization towards M1 profile with the increase of microbicide activity against intracellular pathogen L. mexicana. PPAR activation induced IL-10 downregulation, whereas the production of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 remained high. Moreover, PPAR agonists treatment induced the deactivation of cPLA2-COX-2-prostaglandins pathway together with an increase in TLR4 expression, all of whose criteria meet the M1 macrophage profile. Finally, parasite burden, in treated macrophages, was lower than that in infected nontreated macrophages, most probably associated with the increase of respiratory burst in these treated cells. Based on the above data, we conclude that PPAR agonists used in this work induces M1 macrophages polarization via inhibition of cPLA2 and the increase of aggressive microbicidal activity via reactive oxygen species (ROS) production.
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影响因子：
2.2
作者：
Matte, C;Maion, G;Olivier, M
通讯作者：
Olivier, M
影响因子：
4.4
作者：
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通讯作者：
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影响因子：
2.9
作者：
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通讯作者：
Chakraborty, Sharmistha
影响因子：
4.8
作者：
Faour, WH;Alaaeddine, N;Di Battista, JA
通讯作者：
Di Battista, JA
影响因子：
3.4
作者：
Dermine, JF;Goyette, G;Desjardins, M
通讯作者：
Desjardins, M