Membrane translocation of transient receptor potential ankyrin 1 induced by inflammatory cytokines in lung cancer cells.
Membrane translocation of transient receptor potential ankyrin 1 induced by inflammatory cytokines in lung cancer cells.
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DOI：
10.1016/j.bbrc.2017.06.082
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发表时间：
2017-08
影响因子：
3.1
通讯作者：
Kenji Takahashi;T. Ohta
中科院分区：
文献类型：
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作者：
Kenji Takahashi;T. Ohta
瞬时受体潜在锚蛋白1(TRPA1)是在感觉神经元表达的伤害性感受器之一。它还在炎症部位的非神经细胞中发挥作用。然而，炎症条件下TRPA1在这些细胞中的活性调节机制尚不清楚。为了阐明这些机制，我们检测了炎性细胞因子(IL-1α、IL-1β和肿瘤坏死因子α[肿瘤坏死因子α])对内源性表达TRPA1的肺癌细胞株A549中TRPA1活性和表达的影响。用IL-1α处理，而不是IL-1β或肿瘤坏死因子α处理，以剂量和时间依赖的方式增加了细胞对TRPA1激动剂异硫氰酸烯丙酯的反应。细胞外调节激酶(ERK)抑制剂(PD98059)可抑制IL-1α诱导的TRPA1反应性增加，但不能被Fc-jun激酶、p38丝裂原活化蛋白激酶或磷脂酰肌醇-3激酶的抑制剂所抑制。在IL-1α处理的细胞中，ERK在短暂诱导后24小时，其磷酸化程度逐渐增加。IL-1α使生物素标记的细胞表面蛋白上的TRPA1水平升高。这些结果表明，IL-1α通过激活ERK促进了TRA1向质膜的转位。在炎症条件下，TRPA1可能对非神经性肺细胞具有病理生理作用。
Transient receptor potential ankyrin 1 (TRPA1) is known as one of the nociceptors expressed in sensory neurons. It also plays a role in non-neural cells in inflammatory sites. However, the regulatory mechanisms for the reactivity of TRPA1 in these cells under inflammatory conditions are not clear. To clarify these mechanisms, we examined the effects of inflammatory cytokines (interleukin [IL]-1α, IL-1β and tumor necrosis factor α [TNFα]) on TRPA1 reactivity and expression in the endogenously TRPA1-expressing lung tumor cell line A549. Treatment with IL-1α, but not IL-1β or TNFα, increased the number of cells responding to allyl isothiocyanate, a TRPA1 agonist, in a dose- and time-dependent manner. The IL-1α-induced increase of TRPA1 responsiveness was inhibited by an extracellular-regulated kinase (Erk) inhibitor (PD98059) but not by inhibitors ofc-Jun kinase, p38 mitogen-activated protein kinase or phosphatidylinositol-3 kinase. Phosphorylation of Erk gradually increased at 24 h after its transient induction in cells treated with IL-1α. IL-1α increased the TRPA1 levels on biotinylated cell surface proteins. These results suggest that IL-1α enhances the translocation of TRPA1 to the plasma membrane via the activation of Erk in A549. TRPA1 may have a pathophysiological role in non-neural lung cells under inflammatory conditions.