Maślanka Tomasz, Spodniewska Anna, Barski Dariusz, Jasiecka Agnieszka, Zuśka-Prot Monika, Ziółkowski Hubert, Markiewicz Włodzimierz, Jaroszewski Jerzy Jan
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
Vet Immunol Immunopathol. 2014 Aug 15;160(3-4):192-200. doi: 10.1016/j.vetimm.2014.05.003. Epub 2014 May 16.
A crucial event in the initiation of an immune response is the activation of T cells, which requires IL-2 binding to its high-affinity IL-2 receptor for optimal signaling. The IL-2 receptor α-chain (CD25) is needed for the high affinity binding of IL-2 to effector cells and is potently induced after T cell activation. The aim of this research has been to determine whether prostaglandin E2 (PGE2) affects the CD25 expression on bovine T cells, and if it does, then which of the PGE2 receptor (EP) subtype(s) mediate(s) this effect. Herein, we report that exposure of peripheral blood mononuclear cells (PBMC) to PGE2 considerably reduces the percentage and absolute counts of CD25(+)CD4(+), CD25(+)CD8(+) and CD25(+)WC1(+) T cells, significantly increases the value of these parameters with respect of CD25(-)CD4(+), CD25(-)CD8(+) and CD25(-)WC1(+) T cells, and does not affect counts of the total populations of CD4(+), CD8(+) and WC1(+) T cells. These results indicate that PGE2 down-regulates the CD25 expression on bovine T cells. Moreover, we show that the selective blockade of EP4 receptor, but not EP1 and EP3 receptors, prevents this effect. Interestingly, the exposure of PBMC to a selective EP2 receptor agonist leads to a substantial increase in the percentage and absolute number of CD25(+)CD4(+), CD25(+)CD8(+) and CD25(+)WC1(+) T cells. In conclusions, the PGE2-induced down-regulation of CD25 expression on bovine CD4(+), CD8(+) and WC1(+) T cells should be considered as immunosuppressive and anti-inflammatory action, because these lymphocytes primarily represent effector cells and adequate CD25 expression is essential for their correct functioning. The PGE2-mediated down-regulation of the CD25 expression on bovine T cells is mediated via the EP4 receptor, although selective activation of the EP2 receptor up-regulates the CD25 expression on these cells. Thus, with respect to the effect of PGE2 on the CD25 expression on bovine T cells, EP4 receptor serves as an inhibitory receptor, whereas EP2 receptor functions as a stimulatory receptor. The fact that non-selective stimulation of EP receptors, i.e. triggered by PGE2, leads to weaker CD25 expression proves that inhibitory actions prevail over stimulatory ones. These results indicate the possibility of pharmacological manipulation of the CD25 expression on T cells via selective antagonists and agonists of EP2 and EP4 receptors.
免疫反应启动过程中的一个关键事件是T细胞的激活，这需要白细胞介素-2（IL-2）与其高亲和力的IL-2受体结合以实现最佳信号传导。IL-2受体α链（CD25）是IL-2与效应细胞高亲和力结合所必需的，并且在T细胞激活后被强力诱导。本研究的目的是确定前列腺素E2（PGE2）是否影响牛T细胞上CD25的表达，如果有影响，那么是哪种PGE2受体（EP）亚型介导了这种效应。在此，我们报告外周血单个核细胞（PBMC）暴露于PGE2会显著降低CD25(+)CD4(+)、CD25(+)CD8(+)和CD25(+)WC1(+) T细胞的百分比和绝对计数，相对于CD25(-)CD4(+)、CD25(-)CD8(+)和CD25(-)WC1(+) T细胞，这些参数的值显著增加，并且不影响CD4(+)、CD8(+)和WC1(+) T细胞总群体的计数。这些结果表明PGE2下调了牛T细胞上的CD25表达。此外，我们表明选择性阻断EP4受体而非EP1和EP3受体可阻止这种效应。有趣的是，PBMC暴露于选择性EP2受体激动剂会导致CD25(+)CD4(+)、CD25(+)CD8(+)和CD25(+)WC1(+) T细胞的百分比和绝对数量大幅增加。总之，PGE2诱导的牛CD4(+)、CD8(+)和WC1(+) T细胞上CD25表达的下调应被视为免疫抑制和抗炎作用，因为这些淋巴细胞主要代表效应细胞，而适当的CD25表达对其正常功能至关重要。PGE2介导的牛T细胞上CD25表达的下调是通过EP4受体介导的，尽管选择性激活EP2受体会上调这些细胞上的CD25表达。因此，就PGE2对牛T细胞上CD25表达的影响而言，EP4受体作为抑制性受体，而EP2受体起刺激性受体的作用。EP受体的非选择性刺激（即由PGE2触发）导致较弱的CD25表达这一事实证明抑制作用胜过刺激作用。这些结果表明通过EP2和EP4受体的选择性拮抗剂和激动剂对T细胞上CD25表达进行药理学操纵的可能性。
