Inhibition of protein tyrosine phosphatases prevents mesenteric lymph node T-cell suppression following alcohol intoxication and burn injury.
Inhibition of protein tyrosine phosphatases prevents mesenteric lymph node T-cell suppression following alcohol intoxication and burn injury.
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抑制蛋白酪氨酸磷酸酶可防止酒精中毒和烧伤后肠系膜淋巴结 T 细胞受到抑制。
DOI：
10.1097/bcr.0b013e318171122c
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Choudhry,MashkoorA
中科院分区：
文献类型：
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作者：
Li,Xiaoling;Schwacha,MartinG;Chaudry,IrshadH;Choudhry,MashkoorA
先前，我们已经表明，烧伤前急性酒精（EtOH）中毒增强了对肠系膜淋巴结t细胞效应反应的抑制。此外，t细胞的抑制伴随着p-38和细胞外信号调节激酶（ERK）激活的降低。本研究检测了蛋白酪氨酸磷酸酶（PTP）在EtOH中毒和烧伤后抑制t细胞p-38、ERK和细胞因子产生中的作用。在烧伤或假性损伤（体表总面积约12.5%或25% [TBSA]）前4小时，用5 ml 20%的EtOH悬浮液灌胃雄性大鼠（约250 g），使其血液EtOH水平达到约100 mg/dl。损伤后1天处死大鼠，测定肠系膜淋巴结t细胞细胞因子（IL-2/IFN-γ）的产生、p-38和ERK的活化。与假体相比，25% TBSA烧伤后t细胞细胞因子产生显著减少，而12.5% TBSA烧伤后t细胞细胞因子产生显著减少。然而，无论烧伤面积百分比如何，接受EtOH和烧伤联合损伤的大鼠的t细胞IL-2/IFN-γ水平均显著降低。此外，我们发现，与假药相比，接受EtOH和12.5% TBSA联合损伤的大鼠t细胞中p-38和ERK-1/2磷酸化显著降低。PTP抑制剂pervanadate （10 μM）对t细胞p-38/ERK抑制有效。对IL-2/IFN-γ产生的抑制作用在培养的t细胞中也被减弱。这些发现表明，PTP活性的增加可能有助于EtOH中毒和烧伤后t细胞的抑制。
Previously, we have shown that acute alcohol (EtOH) intoxication before burn injury potentiates the suppression of mesenteric lymph node T-cell effector responses. Moreover, the suppression in T-cell was accompanied with a decrease in p-38 and extracellular-signal-regulated kinase (ERK) activation. This study examined the role of protein tyrosine phosphatases (PTP) in suppressed T-cell p-38, ERK, and cytokine production after EtOH intoxication and burn injury. A blood EtOH level of ∼100 mg/dl in male rats (∼250 g) was achieved by gavaging animals with 5 ml of 20% EtOH suspension 4 hours before burn or sham injury (∼12.5% or 25% total body surface area [TBSA]). One day after injury, rats were killed and mesenteric lymph node T-cell cytokine (IL-2/IFN-γ) production, p-38, and ERK activation were measured. As compared with shams, there was a significant decrease in T-cell cytokine production after 25% and not 12.5% TBSA burn injury. However, T-cell IL-2/IFN-γ levels were significantly decreased in rats receiving a combined insult of EtOH and burn injury regardless of the percentage of burn area. Furthermore, we found a significant decrease in p-38 and ERK-1/2 phosphorylation in T-cells of rats receiving a combined insult of EtOH and 12.5% TBSA burn compared with shams. Treatment of cells with PTP inhibitor pervanadate (10 μM) prevented T-cell p-38/ERK suppression. The suppression in IL-2/IFN-γ production was also attenuated in T-cells cultured in the presence of pervanadate. These findings suggest that an increase in PTP activity may contribute to T-cell suppression after EtOH intoxication and burn injury.