Reduction of T cell-derived ghrelin enhances proinflammatory cytokine expression: implications for age-associated increases in inflammation
Reduction of T cell-derived ghrelin enhances proinflammatory cytokine expression: implications for age-associated increases in inflammation
复制标题
DOI：
10.1182/blood-2008-09-181255
复制
发表时间：
2009-05-21
期刊：
影响因子：
20.3
通讯作者：
Taub, Dennis D.
中科院分区：
文献类型：
--
作者：
Dixit, Vishwa D.;Yang, Hyunwon;Taub, Dennis D.
生长激素释放肽（Ghrelin，Grln）是一种肽类激素，主要在胃中产生，刺激食欲并诱导生长激素（GH）释放。我们以前曾报道，生长激素释放肽也在T细胞中表达，并发挥prothymic和抗炎作用。然而，T细胞来源的ghrelin的生物学相关性仍有待确定。在这里，我们报告说，酰化的生物活性生长素释放肽在人类T细胞中表达，并优先隔离在TCR连接后的脂筏结构域。RNA干扰（RNAi）介导的原代人T细胞中ghrelin的下调激活IkB，并增加Th 1细胞因子和IL-17分泌。在脾脏和T细胞中生长素释放肽表达随着年龄的增加而下降，并且在老年小鼠中给予外源性生长素释放肽减少促炎细胞因子。这些发现表明ghrelin以自分泌和旁分泌的方式调节人和鼠T细胞中促炎细胞因子的表达，并可能有助于调节“炎症-衰老”。”（血。2009; 113：5202-5205）
Ghrelin (Grln) is a peptide hormone that is predominantly produced in the stomach and stimulates appetite and induces growth hormone (GH) release. We have previously reported that ghrelin is also expressed in T cells and exerts prothymic and anti-inflammatory effects. However, the biologic relevance of T cell-derived ghrelin remains to be determined. Here, we report that acylated-bioactive ghrelin is expressed in human T cells and preferentially segregates within the lipid raft domains upon TCR ligation. The RNA interference (RNAi)-mediated down-regulation of ghrelin in primary human T cells activates IkB, and increases Th1 cytokines and IL-17 secretion. Ghrelin expression declines with increasing age in spleen and T cells and exogenous ghrelin administration in old mice reduces proinflammatory cytokines. These findings demonstrate that ghrelin functions in an autocrine and paracrine capacity to regulate proinflammatory cytokine expression in human and murine T cells and may contribute in regulating "inflamm-aging." (Blood. 2009; 113: 5202-5205)