Toll-like receptor ligands induce cytokine and chemokine production in human inner ear endolymphatic sac fibroblasts.
Toll-like receptor ligands induce cytokine and chemokine production in human inner ear endolymphatic sac fibroblasts.
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DOI：
10.1016/j.anl.2016.10.007
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发表时间：
2017-08
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影响因子：
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通讯作者：
Takechiyo Yamada;K. Ogi;M. Sakashita;Masafumi Kanno;Seita Kubo;Yumi Ito;Y. Imoto;Takahiro Tokunaga;Masayuki Okamoto;N. Narita;S. Fujieda
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作者：
Takechiyo Yamada;K. Ogi;M. Sakashita;Masafumi Kanno;Seita Kubo;Yumi Ito;Y. Imoto;Takahiro Tokunaga;Masayuki Okamoto;N. Narita;S. Fujieda
与最近关于小鼠或大鼠内耳细胞中细胞因子或趋化因子的报道相比，人类内耳细胞是否会产生细胞因子或趋化因子几乎是未知的。我们已经首次建立了人内耳来源的成纤维细胞从endolymphatics.MethodsThe Toll样受体（TLR）在人endolymphaticsac成纤维细胞的表达水平，和细胞因子或趋化因子的TLR配体的生产的影响进行了检查。为了证明参与调节精氨酸生产的细胞内途径，我们使用c-Jun N-末端激酶（JNK），细胞外信号相关激酶（ERK），p38丝裂原活化蛋白激酶（p38 MAPK）信号和N-乙酰基-L-半胱氨酸（NAC.ResultsTLR 2，3，4和9的特异性抑制剂在人内淋巴囊成纤维细胞中高度表达。TLR 3配体聚肌苷酸-聚胞苷酸（poly（I：C））显著增强胸腺基质淋巴细胞生成素（TSLP）、B淋巴细胞刺激因子（BLyS）、IFNγ诱导蛋白10（IP-10）和巨噬细胞炎性蛋白1 α（MIP-1α）的分泌。JNK的抑制剂强烈地减少poly（I：C）诱导的TSLP产生。抗氧化剂药物，NAC也减少了TSLP的生产与poly（I：C）。ConclusionOur研究结果表明，人内耳内淋巴囊来源的成纤维细胞可以产生细胞因子和趋化因子响应TLR配体，并发挥一定的作用，在启动免疫反应。
ObjectiveAgainst recent reports concerning cytokine or chemokine in mouse or rat inner ear cells, it is almost unknown whether human inner ear cells would produce cytokine or chemokine. We have for the first time established the human inner-ear-derived fibroblasts from endolymphatic sac.MethodsThe expression levels of Toll-like receptors (TLRs) in human endolymphatic sac fibroblasts, and the effect on cytokine or chemokine production of the TLR ligands have been examined. To demonstrate the intracellular pathways involved in the regulation of cytokine-production, we used specific inhibitors of c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK)-signaling and N-acetyl-l-cysteine (NAC).ResultsTLR 2, 3, 4 and 9 were highly expressed in human endolymphatic sac fibroblasts. The TLR 3 ligand, polyinosinic–polycytidylic acid (poly(I:C)) significantly enhanced the secretion of thymic stromal lymphopoietin (TSLP), B lymphocyte stimulator (BLyS), IFNγ-inducible protein 10 (IP-10), and macrophage inflammatory protein 1 alpha (MIP-1α) from the cells. The inhibitor of JNK strongly reduced the poly(I:C)-induced TSLP-production. The antioxidant drug, NAC also reduced the TSLP-production in fibroblasts stimulated with poly(I:C).ConclusionOur findings suggest human inner-ear-endolymphatic sac derived fibroblasts can produce the cytokine and chemokine in response to TLR ligands and play a certain role during the initiation of an immune response.