首页> 外文期刊>American Journal of Physiology >Shockwaves increase T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation.
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Shockwaves increase T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation.

机译:冲击波通过ATP释放,P2X7受体和FAK活化来增加T细胞增殖和IL-2表达。

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Shockwaves elicited by transient pressure disturbances are used to treat musculoskeletal disorders. Previous research has shown that shockwave treatment affects T-cell function, enhancing T-cell proliferation and IL-2 expression by activating p38 mitogen-activated protein kinase (MAPK) signaling. Here we investigated the signaling pathway by which shockwaves mediate p38 MAPK phosphorylation. We found that shockwaves at an intensity of 0.18 mJ/mm(2) induce the release of extracellular ATP from human Jurkat T-cells at least in part by affecting cell viability. ATP released into the extracellular space stimulates P2X7-type purinergic receptors that induce the activation of p38 MAPK and of focal adhesion kinase (FAK) by phosphorylation on residues Tyr397 and Tyr576/577. Elimination of released ATP with apyrase or inhibition of P2X7 receptors with the antagonists KN-62 or suramin significantly weakens FAK phosphorylation, p38 MAPK activation, IL-2 expression, and T-cell proliferation. Conversely, addition of exogenous ATP causes phosphorylation of FAK and p38 MAPK. Silencing of FAK expression also reduces these cell responses to shockwave treatment. We conclude that shockwaves enhance p38 MAPK activation, IL-2 expression, and T-cell proliferation via the release of cellular ATP and feedback mechanisms that involve P2X7 receptor activation and FAK phosphorylation.
机译:由瞬态压力扰动引起的冲击波用于治疗肌肉骨骼疾病。先前的研究表明,冲击波治疗会通过激活p38促分裂原活化蛋白激酶(MAPK)信号传导来影响T细胞功能,增强T细胞增殖和IL-2表达。在这里,我们调查了冲击波介导p38 MAPK磷酸化的信号传导途径。我们发现,强度为0.18 mJ / mm(2)的冲击波至少部分地通过影响细胞活力来诱导人Jurkat T细胞释放细胞外ATP。释放到细胞外空间中的ATP刺激P2X7型嘌呤能受体,通过在残基Tyr397和Tyr576 / 577上进行磷酸化来诱导p38 MAPK和粘着斑激酶(FAK)的激活。用腺苷三磷酸消除释放的ATP或用拮抗剂KN-62或苏拉明抑制P2X7受体,可显着减弱FAK磷酸化,p38 MAPK激活,IL-2表达和T细胞增殖。相反,外源ATP的添加会导致FAK和p38 MAPK磷酸化。 FAK表达的沉默也减少了这些细胞对冲击波处理的反应。我们得出的结论是,冲击波通过释放细胞ATP和涉及P2X7受体激活和FAK磷酸化的反馈机制来增强p38 MAPK激活,IL-2表达和T细胞增殖。

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