Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock protein 72 in human peripheral blood mononuclear cells.
Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock protein 72 in human peripheral blood mononuclear cells.
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DOI：
10.1016/s0899-9007(02)00839-0
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发表时间：
2003
期刊：
影响因子：
4.4
通讯作者：
P. Wischmeyer;Jacob J. Riehm;K. Singleton;H. Ren;M. Musch;M. Kahana;E. Chang
中科院分区：
文献类型：
--
作者：
P. Wischmeyer;Jacob J. Riehm;K. Singleton;H. Ren;M. Musch;M. Kahana;E. Chang
目的肿瘤坏死因子-α等促炎细胞因子的过度表达可导致危重病患者发生多器官功能障碍综合征和感染性休克。我们先前在体内实验中发现谷氨酰胺(Gln)可以抑制细胞因子的表达，诱导热休克蛋白72(HSP72)，并对内毒素诱导的死亡和器官损伤具有保护作用。然而，谷氨酰胺对人外周血多形核细胞(PBMC)细胞因子释放和热休克蛋白72(HSP72)表达的直接抑制作用的研究尚不多见。用不同剂量的谷氨酰胺处理人外周血单核细胞后，用脂多糖(LPS)刺激。结果SGLN剂量大于4 mM时，内毒素刺激后4h和2 4h，肿瘤坏死因子α的释放明显减少。内毒素前亚致死温度可显著降低内毒素后的肿瘤坏死因子-α。剂量大于2~4 mM的Gln可导致LPS后HSP72表达增加。结论Gln可直接抑制PBMC中促炎细胞因子的释放，可能改善危重患者的预后。这种作用可能与HSP72表达增强有关。
OBJECTIVESOverexpression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) can contribute to multiple organ dysfunction syndrome and septic shock in critically ill patients. We previously found that glutamine (GLN) can attenuate cytokine expression, induce heat shock protein 72 (HSP 72), and protect against endotoxin-induced mortality and organ injury in an in vivo rat model. However, data on the effect of GLN on direct attenuation of cytokine release and HSP 72 expression in human peripheral blood polymorphonuclear cells (PBMCs) is lacking.METHODSIn this study, we assessed the effect of GLN on TNF-α and HSP 72 expression in human PBMCs. After treating with various doses of GLN, human PBMCs were stimulated with lipopolysaccharide (LPS). TNF-α release was analyzed via enzyme-linked immunosorbent assay and HSP 72 via western blot.RESULTSGLN at doses greater than 4 mM decreased TNF-α release at 4 and 24 h after LPS stimulation. Sublethal heating of PBMCs before LPS also markedly decreased TNF-α after LPS. Doses of GLN greater than 2 to 4 mM led to an increase in HSP 72 expression after LPS.CONCLUSIONSThese results indicate that GLN, which may improve outcomes in critically ill patients, can directly attenuate pro-inflammatory cytokine release in PBMCs. This effect may be related to enhanced HSP 72 expression.