ERK and Not p38 Pathway Is Required for IL-12 Restoration of T Cell IL-2 and IFN-γ in a Rodent Model of Alcohol Intoxication and Burn Injury
ERK and Not p38 Pathway Is Required for IL-12 Restoration of T Cell IL-2 and IFN-γ in a Rodent Model of Alcohol Intoxication and Burn Injury
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DOI：
10.4049/jimmunol.0804103
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发表时间：
2009-09-15
影响因子：
4.4
通讯作者：
Choudhry, Mashkoor A.
中科院分区：
文献类型：
--
作者：
Li, Xiaoling;Chaudry, Irshad H.;Choudhry, Mashkoor A.
我们实验室先前的研究表明，急性酒精/乙醇（EtOH）中毒结合烧伤通过抑制p38和ERK激活抑制T细胞IL-2和IFN-γ的产生。由于IL-12在Th 1分化和IFN-γ产生中起主要作用，我们研究了乙醇加烧伤后IL-2和IFN-γ产生的减少是否是由于IL-12的减少。此外，我们研究了IL-12是否利用p38/ERK通路来调节EtOH和烧伤后T细胞IL-2和IFN-γ的产生。雄性大鼠（类似于250 g）在类似于12.5%总体表面积烧伤或假损伤前4 h用5 ml 20% EtOH管饲。伤后第1天处死大鼠，分离肠系膜淋巴结T细胞。在不存在或存在rIL-12（10 ng/ml）的情况下用抗CD 3刺激T细胞5分钟并裂解。使用特异性Abs和Western印迹分析裂解物的p38/ERK蛋白和磷酸化水平。在一些实验中，在有或没有p38（10 μ M SB 203580/SB 202190）或ERK（50 μ M PD 98059）抑制剂的情况下培养T细胞48小时，以描述p38和ERK在IL-12介导的IL-2和IFN-γ恢复中的作用。我们的研究结果表明，IL-12使T细胞中的p38和ERK活化正常化，但使用p38和ERK抑制剂获得的结果表明，ERK的恢复在EtOH和烧伤后IL-12介导的T细胞IL-2和IFN-γ产生的恢复中起主要作用。免疫学杂志，2009，183：3955-3962.
Previous studies from our laboratory have shown that acute alcohol/ethanol (EtOH) intoxication combined with burn injury suppresses T cell IL-2 and IFN-gamma production by inhibiting p38 and ERK activation. Because IIL-12 plays a major role in Th1 differentiation and IFN-gamma production, we examined whether diminished IL-2 and IFN-gamma production after EtOH plus burn injury resulted from a decrease in IL-12. Furthermore, we investigated whether IL-12 utilizes the p38/ERK pathway to modulate T cell IL-2 and IFN-gamma production after EtOH and burn injury. Male rats (similar to 250 g) were gavaged with 5 ml of 20% EtOH 4 h before similar to 12.5% total body surface area burn or sham injury. Rats were sacrificed on day 1 after injury, and mesenteric lymph node T cells were isolated. T cells were stimulated with anti-CD3 in the absence or presence of rIL-12 (10 ng/ml) for 5 min and lysed. Lysates were analyzed for p38/ERK protein and phosphorylation levels using specific Abs and Western blot. In some experiments, T cells were cultured for 48 h with or without the inhibitors of p38 (10 mu M SB203580/SB202190) or ERK (50 mu M PD98059) to delineate the role of p38 and ERK in IL-12-mediated restoration of IL-2 and IFN-gamma. Our findings indicate that IL-12 normalizes both p38 and ERK activation in T cells, but the results obtained using p38 and ERK inhibitors indicate that the restoration of ERK plays a predominant role in IL-12-mediated restoration of T cell IL-2 and IFN-gamma production after EtOH and burn injury. The Journal of Immunology, 2009,183: 3955-3962.