Prostaglandin E2 suppressed IL-15-mediated human NK cell function through down-regulation of common γ-chain
Prostaglandin E2 suppressed IL-15-mediated human NK cell function through down-regulation of common γ-chain
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DOI：
10.4049/jimmunol.166.2.885
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发表时间：
2001-01-15
影响因子：
4.4
通讯作者：
Jones, Q
中科院分区：
文献类型：
--
作者：
Joshi, PC;Zhou, XC;Jones, Q
NK细胞功能受细胞因子和某些生化介质以正或负方式调节。本研究旨在探讨PGE（2）对IL-15激活的人NK细胞功能的抑制作用。将纯化的NK细胞与200 ng/ml IL-15在存在或不存在10-200 ng/ml PGE（2）的情况下培养2天，PGE（2）在分泌和转录水平上显著抑制NK细胞介导的细胞毒性和IFN-γ的产生。我们还评估了PGE（2）对IL-15 R复合物的作用，该复合物由IL-2 R β、共同γ链（γ（c）链）和特异性链IL-15 α组成。IL-15处理后，γ（c）链的阳性细胞百分比和结合位点数显著增加，而PGE（2）联合处理后，γ（c）链的阳性细胞百分比和结合位点数显著减少。相比之下，IL-15处理后IL-2 R β的组成型表达显著降低，在PGE存在下未检测到变化（2）。在转录水平上，IL-15和PGE（2）对β-或γ（c）-链的表达都没有显著影响。IL-15处理后8 h，IL-15 α在转录水平的表达增加了3倍，达到峰值;然而，PGE（2）没有显著影响。PGE（2）对NK功能的抑制不是由于NK细胞内源性产生IL-4、IL-10或TGF-β（1）。这些结果表明，NK细胞表面γ（c）链表达的下调可能是PGE（2）介导IL-15激活的NK细胞功能抑制的一种机制。
NK cell function is regulated by cytokines and certain biochemical mediators in a positive or negative manner. This study was performed to investigate the suppressive effects of PGE(2) on IL-15-activated human NK cell function. Purified NK cells were cultured with 200 ng/ml IL-15 for 2 days in the presence or absence of 10-200 ng/ml PGE(2), PGE(2) significantly suppressed NK cell-mediated cytotoxicity and IFN-gamma production at the secretional and the transcriptional levels. We also evaluated the effect of PGE(2) on the IL-15R complex that consists of IL-2R beta, common gamma -chain (gamma (c)-chain), and a specific chain IL-15 alpha. Percentage of positive cells and number of binding sites for gamma (c)-chain were significantly increased after IL-15 treatment; however, a substantial decrease was observed with PGE(2) cotreatment. In contrast, constitutive expression of IL-2R beta was significantly decreased after IL-15 treatment, with no change detected in the presence of PGE(2). At the transcriptional level, neither IL-15 nor PGE(2) had significant effects on the expression of beta- or gamma (c)-chains. There was a 3-fold increase in the expression of IL-15 alpha at the transcriptional level that peaked at 8 h after IL-15 treatment; however, PGE(2) had no significant effect. Suppression of NK function by PGE(2) was not due to the endogenous production of IL-4, IL-10, or TGF-beta (1) by NK cells. These results suggest that down-regulation of surface expression of gamma (c)-chain on NK cells may be one mechanism through which PGE(2) mediates suppression of IL-15-activated NK cell function.