Cutting edge: IL-4-Mediated protection of primary B lymphocytes from apoptosis via stat6-dependent regulation of glycolytic metabolism
Cutting edge: IL-4-Mediated protection of primary B lymphocytes from apoptosis via stat6-dependent regulation of glycolytic metabolism
复制标题
DOI：
10.4049/jimmunol.179.8.4953
复制
发表时间：
2007-10-15
影响因子：
4.4
通讯作者：
Chiles, Thomas C.
中科院分区：
文献类型：
--
作者：
Dufort, Fay J.;Bleiman, Blair F.;Chiles, Thomas C.
IL-4通过上调抗凋亡蛋白如Bcl-x（L）防止幼稚B淋巴细胞的死亡。尽管有研究表明葡萄糖利用与造血细胞的生长因子依赖性存活有关，但葡萄糖能量代谢在IL-4维持B细胞活力中的作用尚不清楚。我们发现IL-4触发脾B细胞中的葡萄糖摄取、Glutl表达和糖酵解;这伴随着细胞ATP的增加。糖酵解抑制导致细胞凋亡，即使在IL-4的存在下。IL-4诱导的糖酵解通常发生在胰岛素受体底物-2或PI 3 K的p85 α亚基缺陷的B细胞中，并且不受PI 3 K或MAWK途径抑制剂预处理的影响。Stat 6缺陷型B细胞表现出IL-4诱导的糖酵解受损。细胞可渗透的组成型活性Stat 6可有效恢复Stat 6缺陷型B细胞中IL-4诱导的糖酵解。因此，除了控制抗凋亡蛋白，IL-4介导B细胞的存活通过调节葡萄糖能量代谢通过Stat 6依赖性途径。
IL-4 prevents the death of naive B lymphocytes through the up-regulation of antiapoptotic proteins such as Bcl-x(L). Despite studies implicating glucose utilization in growth factor-dependent survival of hemopoietic cells, the role of glucose energy metabolism in maintaining B cell viability by IL-4 is unknown. We show that IL-4 triggers glucose uptake, Glutl expression, and glycolysis in splenic B cells; this is accompanied by increased cellular ATP. Glycolysis inhibition results in apoptosis, even in the presence of IL-4. IL-4-induced glycolysis occurs normally in B cells deficient in insulin receptor substrate-2 or the p85 alpha subunit of PI3K and is not affected by pretreatment with PI3K or MAWK pathway inhibitors. Stat6-deficient B cells exhibit impaired IL-4-induced glycolysis. Cell-permeable, constitutively active Stat6 is effective in restoring IL-4-induced glycolysis in Stat6-deficient B cells. Therefore, besides controlling antiapoptotic proteins, IL-4 mediates B cell survival by regulating glucose energy metabolism via a Stat6-dependent pathway.