TLR3 activation evokes IL-6 secretion, autocrine regulation of Stat3 signaling and TLR2 expression in human bronchial epithelial cells
TLR3 activation evokes IL-6 secretion, autocrine regulation of Stat3 signaling and TLR2 expression in human bronchial epithelial cells
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DOI：
10.1007/s12079-012-0185-z
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发表时间：
2013-06-01
影响因子：
4.1
通讯作者：
O'Grady, Scott M.
中科院分区：
文献类型：
--
作者：
Melkamu, Tamene;Kita, Hirohito;O'Grady, Scott M.
暴露于合成的双链RNA（poly I：C）的人支气管上皮细胞表现出IL-6和RANTES分泌增加以及TLR 2表达在TLR 3沉默后被抑制。暴露于poly I：C后检测到NF-κ B和Stat 3磷酸化增加，用靶向IL-6受体α的中和抗体（IL-6 R alpha-nAb）或阻断Jak 2和Stat 3活性的预处理抑制了Stat 3磷酸化。IL-6 R α-nAb和Jak 2、Stat 3和NF-κ B磷酸化抑制剂也降低了poly I：C对TLR 2的上调，而RANTES分泌不受影响，但在NF-κ B抑制后被消除。外源性IL-6治疗未能增加TLR 2。这些发现表明，TLR 3活化通过涉及IL-6分泌、IL-6 R α活化和随后的Stat 3磷酸化的自分泌信号传导差异调节TLR表达。结果还表明，NF-κ B和Stat 3是TLR 2的TLR 3依赖性上调所必需的，并且其延迟表达是由于IL-6依赖性Stat 3活化的需要。
Human bronchial epithelial cells exposed to synthetic double-stranded RNA (poly I: C) exhibited increased IL-6 and RANTES secretion and TLR2 expression that was inhibited following TLR3 silencing. Increased NF-kappa B and Stat3 phosphorylation were detected after poly I: C exposure and pretreatment with neutralizing antibody targeting IL-6 receptor alpha (IL-6R alpha-nAb) or blocking Jak2 and Stat3 activity inhibited Stat3 phosphorylation. TLR2 up-regulation by poly I: C was also reduced by IL-6R alpha-nAb and inhibitors of Jak2, Stat3 and NF-kappa B phosphorylation, whereas RANTES secretion was unaffected, but abolished following NF-kappa B inhibition. Treatment with exogenous IL-6 failed to increase TLR2. These findings demonstrate that TLR3 activation differentially regulates TLR expression through autocrine signaling involving IL-6 secretion, IL-6R alpha activation and subsequent phosphorylation of Stat3. The results also indicate that NF-kappa B and Stat3 are required for TLR3 dependent up-regulation of TLR2 and that its delayed expression was due to a requirement for IL-6-dependent Stat3 activation.