IL-17A stimulates granulocyte colony-stimulating factor production via ERK1/2 but not p38 or JNK in human renal proximal tubular epithelial cells
IL-17A stimulates granulocyte colony-stimulating factor production via ERK1/2 but not p38 or JNK in human renal proximal tubular epithelial cells
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DOI：
10.1152/ajprenal.00113.2011
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Akizawa, Tadao
中科院分区：
文献类型：
--
作者：
Hirai, Yuki;Iyoda, Masayuki;Akizawa, Tadao
Hirai Y，Iyoda M，Shibata T，Kuo Y，Kawaguchi M，Hizawa N，MatSumoto K，Wada Y，Kokubu F，Akizawa T。IL-17A通过ERK1/2刺激人肾近端小管上皮细胞产生粒细胞集落刺激因子，但不刺激p38或JNK。AM J Physiol Renal Physiol 302：F244-F250,2012。2011年10月12日首次出版；DOI：10.1152/ajprenal.00113.2011。-我们研究了IL-17A在诱导人肾近端小管上皮细胞产生粒细胞集落刺激因子(G-CSF)的潜在作用。以人肾近端小管上皮细胞(HK-2，ATCC)为研究对象，采用ELISA法、实时定量RT-PCR法和免疫印迹法检测IL-17A和IL-17F对G-CSF产生的影响。用流式细胞仪检测细胞表面IL-17受体(IL-17Rs)的表达。IL-17A刺激近端肾小管上皮细胞后，G-CSF的分泌呈剂量和时间依赖性增加。这种作用依赖于mRNA转录和蛋白质翻译。实时荧光定量RT-PCR结果显示，IL-17A刺激后6h，G-CSF mRNA表达达到最高水平，且呈剂量依赖性。IL-17RA和IL-17RC均表达于近端肾小管上皮细胞。IL-17A还可促进细胞分泌由肿瘤坏死因子-α或白细胞介素1-β介导的G-CSF。此外，IL-17A可诱导MAPK(ERK1/2，但不能激活p38 MAPK或JNK)，而药物抑制剂MEK1/2(U0126)，但不能抑制p38 MAPK(SB203580)或JNK(SP600125)，可显著阻断IL-17A介导的G-CSF释放。我们证实了IL-17A在肾小管上皮细胞中诱导G-CSF的潜在能力。提示在肾小管损伤中，IL-17A可能通过刺激G-CSF在中性粒细胞迁移和活化中发挥重要作用。
Hirai Y, Iyoda M, Shibata T, Kuno Y, Kawaguchi M, Hizawa N, Matsumoto K, Wada Y, Kokubu F, Akizawa T. IL-17A stimulates granulocyte colony-stimulating factor production via ERK1/2 but not p38 or JNK in human renal proximal tubular epithelial cells. Am J Physiol Renal Physiol 302: F244-F250, 2012. First published October 12, 2011; doi:10.1152/ajprenal.00113.2011.-We investigated the potential role of IL-17A in the induction of granulocyte colony-stimulating factor (G-CSF), a critical granulopoietic growth factor, in human renal proximal tubular epithelial cells. Human renal proximal tubular cells (HK-2, ATCC) were used to characterize the effects of IL-17A or IL-17F on G-CSF production, using ELISA, real-time RT-PCR, and immunoblotting. The cell surface expression of IL-17 receptors (IL-17Rs) was analyzed by flow cytometry. IL-17A stimulation of proximal tubular cells led to a dose-and time-dependent increase in secreted G-CSF. This effect was dependent on mRNA transcription and protein translation. Real-time RT-PCR demonstrated that G-CSF mRNA expression reached a maximum level at 6 h following IL-17A stimulation and that this increase was dose dependent. Both IL-17RA and IL-17RC were expressed on proximal tubular cells. IL-17A also enhanced TNF-alpha- or IL-1 beta-mediated G-CSF secretion from cells. Additionally, IL-17A induced MAPK (ERK1/2 but not p38 MAPK or JNK) activation, and pharmacological inhibitors of MEK1/2 (U0126) but not of p38 MAPK (SB203580) or JNK (SP600125), significantly blocked the IL-17A-mediated G-CSF release. We demonstrated the potential ability of IL-17A to induce G-CSF in renal proximal tubular cells. It is proposed that IL-17A may play an important role in neutrophil transmigration and activation via stimulation of G-CSF in tubular injury.