Liang Mengfan, Wang Xuemin, Yuan Yuan, Zhou Quanhong, Tong Chuanyao, Jiang Wei
Department of Anesthesiology/Intensive Care Unit, 6th Municipal Hospital, Medical College of Shanghai Jiao Tong University, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2009 Feb;41(2):171-7. doi: 10.1093/abbs/gmn020.
Macrophage plays a vital role in sepsis. However, the modulatory effect of glutamine (Gln) on macrophage/ monocyte-mediate cytokines release is still controversial. Thus, we investigated the effect of Gln on macrophage tumor necrosis factor (TNF)-alpha release and heat shock protein (HSP) 72 expression in vivo and in vitro. Data from our study indicated that the increase of HSP72 expression was significant at 8 mM of Gln 4 h after lipopolysaccharide (LPS) stimulation and became independent of Gln concentrations at 24 h, whereas TNF-alpha release was dose- and time-dependent on Gln. Heat stress (HS) induced more HSP72 and less TNF-alpha production compared with the non-HS group. However, the production of TNF-alpha in cells pretreated with HS was increased with increasing concentrations of Gln. Treatment with various concentrations of Gln for 1 h and then 0.5 mM Gln for 4 h led to an increase in HSP72 expression, but not in TNF-alpha production. In sepsis model mice, Gln treatment led to a significantly lower intracellular TNF-alphalevel and an increase in HSP72 expression in mouse peritoneal macrophages. Our results demonstrate that Gln directly increases TNF-alpha release of LPS-stimulated RAW264.7 macrophages in a dose-dependent manner, and also decreases mouse peritoneal macrophages TNF-a release in the sepsis model. Taken together, our data suggest that there may be more additional pathways by which Gln modulates cytokine production besides HSP72 expression in macrophage during sepsis.
巨噬细胞在脓毒症中起着至关重要的作用。然而，谷氨酰胺（Gln）对巨噬细胞/单核细胞介导的细胞因子释放的调节作用仍存在争议。因此，我们研究了Gln在体内和体外对巨噬细胞肿瘤坏死因子（TNF）-α释放和热休克蛋白（HSP）72表达的影响。我们的研究数据表明，在脂多糖（LPS）刺激后4小时，8 mM的Gln可使HSP72表达显著增加，而在24小时时则与Gln浓度无关，而TNF-α释放则呈剂量和时间依赖性。与非热应激组相比，热应激（HS）诱导产生更多的HSP72和更少的TNF-α。然而，HS预处理细胞中TNF-α的产生随着Gln浓度的增加而增加。用不同浓度的Gln处理1小时，然后用0.5 mM Gln处理4小时，导致HSP72表达增加，但TNF-α产生没有增加。在脓毒症模型小鼠中，Gln处理导致小鼠腹腔巨噬细胞内TNF-α水平显著降低，HSP72表达增加。我们的结果表明，Gln以剂量依赖性方式直接增加LPS刺激的RAW264.7巨噬细胞的TNF-α释放，并且在脓毒症模型中也降低小鼠腹腔巨噬细胞的TNF-α释放。综上所述，我们的数据表明，在脓毒症期间，除了巨噬细胞中HSP72表达外，Gln可能还有更多其他途径调节细胞因子的产生。
