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首页> 外文期刊>Cytokine >CpG-DNA suppresses poly(I:C)-induced TSLP production in human laryngeal arytenoid fibroblasts
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CpG-DNA suppresses poly(I:C)-induced TSLP production in human laryngeal arytenoid fibroblasts

机译:CpG-DNA抑制人喉咽类成纤维细胞中聚(I:C)诱导的TSLP产生

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Thymic stromal lymphopoietin (TSLP) exerts a marked influence on the polarization of dendritic cells to drive T helper (Th) 2 cytokine production, and has been linked to allergic airway diseases. Although TSLP is produced by airway epithelium, TSLP production in laryngeal arytenoid fibroblasts remains largely unexplored. We examined the effect of Toll-like receptor (TLR) ligands and the cross-talk that occurs among different TLR ligands on TSLP production in arytenoid fibroblasts. Since mRNA of TLR 2, 3, 4, and 9 has been found to be expressed in arytenoid fibroblasts, we examined the effect on its production of TLR ligands. TSLP production by arytenoid fibroblasts was strongly induced in the presence of polyinosinic-polycytidylic acid (poly(I:C)), a ligand of TLR3. Its production was synergistically induced in the presence of IL-4, to a level more than 100 times higher than that observed in the absence of poly(I:C) or IL-4. We also revealed that B type DNA containing CpG motifs (CpG-DNA) coding for a TLR9 ligand markedly suppressed both poly(I:C)-induced and poly(I:C)-plus-IL-4-induced TSLP production. B type CpG-DNA decreased the poly(I:C)-induced phosphorylation of c-Jun N-terminal kinase (JNK), and pre-incubation with SP600125 (inhibitor of JNK) reduced the poly(I:C)-induced TSLP-production. These results indicate that human arytenoid fibroblasts strongly induce TSLP production with stimulation by double-stranded RNA (dsRNA), which can be inhibited by CpG-DNA and participate in immune allergic responses.
机译:胸腺基质淋巴细胞生成素(TSLP)对树突状细胞的极化产生显着影响,以驱动T辅助(Th)2细胞因子的产生,并与过敏性气道疾病有关。尽管TSLP是由气道上皮产生的,但是在喉部的类人猿成纤维细胞中TSLP的产生仍未开发。我们检查了Toll样受体(TLR)配体的影响,以及不同的TLR配体之间发生的串扰对类人猿成纤维细胞中TSLP产生的影响。由于已发现TLR 2、3、4和9的mRNA在类癌成纤维细胞中表达,因此我们研究了对其产生TLR配体的影响。在多肌苷-聚胞苷酸(poly(I:C))(一种TLR3的配体)的存在下,强烈诱导了由类人猿成纤维细胞产生的TSLP。在IL-4存在下协同诱导其产生,其水平比在不存在poly(I:C)或IL-4的情况下观察到的水平高100倍以上。我们还揭示了,含有编码TLR9配体的CpG基序(CpG-DNA)的B型DNA显着抑制了poly(I:C)诱导的和poly(I:C)plus-IL-4诱导的TSLP产生。 B型CpG-DNA降低了poly(I:C)诱导的c-Jun N末端激酶(JNK)的磷酸化,与SP600125(JNK抑制剂)的预孵育降低了poly(I:C)诱导的TSLP -生产。这些结果表明,人类的类胡萝卜素成纤维细胞在双链RNA(dsRNA)的刺激下强烈诱导TSLP产生,而双链RNA可以被CpG-DNA抑制并参与免疫过敏反应。

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