Joshi P C, Zhou X, Cuchens M, Jones Q
Departments of. Surgery and Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
J Immunol. 2001 Jan 15;166(2):885-91. doi: 10.4049/jimmunol.166.2.885.
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-2Rbeta, common gamma-chain (gamma(c)-chain), and a specific chain IL-15Ralpha. 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-2Rbeta 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-15Ralpha 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.
自然杀伤（NK）细胞的功能受到细胞因子和某些生化介质的正向或负向调节。本研究旨在探讨前列腺素E2（PGE2）对白细胞介素-15（IL-15）激活的人NK细胞功能的抑制作用。将纯化的NK细胞在有或无10 - 200 ng/ml PGE2的情况下，与200 ng/ml IL-15一起培养2天。PGE2在分泌水平和转录水平上均显著抑制NK细胞介导的细胞毒性和干扰素-γ（IFN-γ）的产生。我们还评估了PGE2对由白细胞介素-2受体β（IL-2Rβ）、共同γ链（γc链）和特异性链IL-15Rα组成的IL-15受体复合物的影响。IL-15处理后，γc链阳性细胞百分比和结合位点数量显著增加；然而，PGE2共同处理后观察到显著下降。相比之下，IL-15处理后IL-2Rβ的组成性表达显著降低，在有PGE2存在的情况下未检测到变化。在转录水平上，IL-15和PGE2对β链或γc链的表达均无显著影响。IL-15处理后8小时，转录水平上IL-15Rα的表达增加了3倍并达到峰值；然而，PGE2没有显著影响。PGE2对NK功能的抑制并非由于NK细胞内源性产生白细胞介素-4（IL-4）、白细胞介素-10或转化生长因子-β1（TGF-β1）。这些结果表明，NK细胞表面γc链表达的下调可能是PGE2介导抑制IL-15激活的NK细胞功能的一种机制。
