TNF-alpha modulates adipose macrophage polarization to M1 phenotype in response to scorpion venom
TNF-alpha modulates adipose macrophage polarization to M1 phenotype in response to scorpion venom
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DOI：
10.1007/s00011-015-0876-z
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发表时间：
2015-11-01
影响因子：
6.7
通讯作者：
Laraba-Djebari, Fatima
中科院分区：
文献类型：
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作者：
Ait-Lounis, Aouatef;Laraba-Djebari, Fatima
我们以前报道过，澳大利亚蝎毒（Aah）及其毒性组分影响脂肪组织代谢。然而，免疫系统的贡献和脂肪组织巨噬细胞（ATMs）在蝎毒诱导的炎症进展中的作用还很不清楚，在这里，我们评估的能力，毒性组分Aah毒（FTox-G50）诱导M1和M2标记基因在脂肪组织和分离的基质血管细胞（SVC）的表达。在注射FTox-G50蛇毒后24 h，对SVC进行实时荧光定量PCR检测IL-12 p40、IL-23和其他巨噬细胞相关标志物的基因表达，发现注射FTox-G50蛇毒的小鼠的ATM显著增加了IL-12 p40和IL-23的表达。此外，一氧化氮合酶2（M1标记）的表达上调，但精氨酸酶1（M2标记）的表达没有。全身注射针对TNF-α结合的化学抑制剂可降低炎症M1巨噬细胞标志物和MAPKpk 2基因的表达，MAPKpk 2基因是炎症信号传导的关键介质，这些结果表明TNF-α是蝎子毒液诱导的炎症和巨噬细胞活化的生理调节剂。
We previously reported that Androctonus australis hector (Aah) venom and its toxic fraction affect adipose tissue metabolism. However, the contribution of immune system and the role of adipose tissue macrophages (ATMs) in the progression of inflammation induced by scorpion venom remain largely unknown.Here we evaluate the capacity of the toxic fraction of Aah venom (FTox-G50) to induce the expression of M1 and M2 markers genes on adipose tissue and isolated stromal vascular cells (SVC). Quantitative real-time PCR was performed on the SVC 24 h after FTox-G50 venom injection to assess the gene expressions of IL12p40, IL23, and other macrophages-associated markers.We found that ATM from FTox-G50-venom-injected mice markedly increased the expressions of IL-12p40 and IL-23. Furthermore, the expression of nitric oxide synthase 2 (an M1 marker) was up-regulated, but the expression of Arginase1 (an M2 marker) was not. Systemic injection of a chemical inhibitor directed against TNF-alpha binding reduced the expression of inflammatory M1 macrophage markers and the MAPKpk2 gene, a key mediator of inflammatory signaling.These results indicate that TNF-alpha is a physiological regulator of inflammation and macrophage activation induced by scorpion venom.