Istradefylline, an adenosine A2a receptor antagonist, inhibits the CD4+T-cell hypersecretion of IL-17A and IL-8 in humans.
Istradefylline, an adenosine A2a receptor antagonist, inhibits the CD4+T-cell hypersecretion of IL-17A and IL-8 in humans.
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Istradefylline 是一种腺苷 A2a 受体拮抗剂，可抑制人类 CD4 T 细胞过度分泌 IL-17A 和 IL-8。
DOI：
10.1080/25785826.2022.2094593
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发表时间：
2022
影响因子：
4.4
通讯作者：
S.
中科院分区：
文献类型：
--
作者：
Tokano,M.;Kawano;M.;Takagi;R.;Matsushita;S.
由三磷酸腺苷产生的胞外腺苷在能量过程、神经传递和炎症反应中发挥作用。Istradeylline是一种选择性腺苷A2a受体(A2aR)拮抗剂，用于治疗帕金森病。我们之前使用小鼠模型显示，腺苷可刺激白细胞介素17AviaA2aR的高分泌，这在小鼠的中性粒细胞炎症模型中起作用。这一发现表明，腺苷是中性粒细胞炎症的内源性调节剂。因此，我们研究了依特拉芬在人体内的体外效应。本研究利用人外周血单个核细胞(PBMCs)，通过混合淋巴细胞反应(MLR)、PBMCs、CD4+T细胞和白色念珠菌抗原(Ag)刺激的PBMCs，检测了腺苷、腺苷受体激动剂和去甲肾上腺素对细胞因子反应的影响。我们发现腺苷和A2aR激动剂(PSB0777)促进人外周血单核细胞产生IL-17A和IL-8，而去甲肾上腺素抑制这一反应。此外，依特拉芬不仅抑制腺苷诱导的IL-17A和IL-8的产生，而且也抑制C诱导的IL-17A和IL-8的产生。白念珠菌抗原刺激的PBMCs。这些结果表明腺苷介导的IL-17A和IL-8的产生在中性粒细胞炎症中起作用，而川地黄碱可能是有效的拮抗剂。
Extracellular adenosine produced from ATP plays a role in energy processes, neurotransmission, and inflammatory responses. Istradefylline is a selective adenosine A2a receptor (A2aR) antagonist used for the treatment of Parkinson's disease. We previously showed using mouse models that adenosine primes hypersecretion of interleukin (IL)-17AviaA2aR, which plays a role in neutrophilic inflammation models in mice. This finding suggests that adenosine is an endogenous modulator of neutrophilic inflammation. We, therefore, investigated thein vitroeffect of istradefylline in humans. In the present study, using human peripheral blood mononuclear cells (PBMCs), we tested the effect of adenosine, adenosine receptor agonists and istradefylline on cytokine responses using mixed lymphocyte reaction (MLR), PBMCs, CD4+T cells, andCandida albicansantigen (Ag)-stimulated PBMCs. We showed that adenosine and an A2aR agonist (PSB0777) promoted IL-17A and IL-8 production from human PBMCs, and istradefylline suppressed this response. In addition, istradefylline inhibited not only the IL-17A and IL-8 production induced by adenosine but also that fromC. albicansAg-stimulated PBMCs. These results indicate that adenosine-mediated IL-17A and IL-8 production plays a role in neutrophilic inflammation, against which istradefylline should be effective.