Hou Yi-Feng, Zhou Yan-Chun, Zheng Xiao-Xuan, Wang Hai-Yan, Fu Yi-Ling, Fang Zhe-Man, He Shao-Heng
Allergy and Inflammation Research Institute, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515041, China.
Mol Immunol. 2006 May;43(12):1982-92. doi: 10.1016/j.molimm.2005.11.013. Epub 2006 Jan 10.
It was reported recently that histamine induced Toll-like receptor (TLR)2 and TLR4 expression in endothelial cells and enhanced their sensitivity to Gram-positive and Gram-negative bacteria; and that TLRs were expressed in airway epithelial cells and that several inflammatory mediators modulated their expression. However, little is known of potential influence of histamine on TLRs in pulmonary epithelial cells. In the present study, effects of histamine on expression of TLRs in both human A549 and NCI-H292 cell lines were examined by using real-time quantitative RT-PCR analysis, flow cytometry and immunofluorescent staining. The results revealed that both cell types constitutively expressed mRNAs for TLR1-TLR10. Histamine up-regulated the expression of TLR3 mRNA by 12.3- and 11.6-fold, respectively in both cell types. The time course showed that histamine induced TLR3 mRNA expression was initiated at 30 min, nearly reached peak levels after 2 h and was sustained at least until 12 h. Histamine also induced TLR3 protein expression in A549 and NCI-H292 cells. Histamine and poly (I:C), a specific TLR3 ligand stimulated interleukin (IL)-8 secretion from both cell types. Moreover, histamine enhanced poly (I:C)-induced IL-8 secretion and phosphorylation of NF-kappaB in the two cell types, and histamine H1 receptor antagonists inhibited the action of histamine. In conclusion, histamine selectively up-regulated expression of TLR3, and stimulated IL-8 secretion from the cells. Histamine also enhanced poly (I:C) induced IL-8 secretion and phosphorylation of NF-kappaB. These observations suggest that histamine might play an important role in enhancing the innate immune responses of airway to viral infection.
最近有报道称，组胺可诱导内皮细胞中Toll样受体（TLR）2和TLR4的表达，并增强其对革兰氏阳性和革兰氏阴性细菌的敏感性；且TLR在气道上皮细胞中表达，多种炎症介质可调节其表达。然而，关于组胺对肺上皮细胞中TLR的潜在影响知之甚少。在本研究中，通过实时定量RT-PCR分析、流式细胞术和免疫荧光染色，检测了组胺对人A549和NCI-H292细胞系中TLR表达的影响。结果显示，两种细胞类型均组成性表达TLR1-TLR10的mRNA。组胺分别使两种细胞类型中TLR3 mRNA的表达上调了12.3倍和11.6倍。时间进程显示，组胺诱导的TLR3 mRNA表达在30分钟时开始，2小时后几乎达到峰值水平，并至少持续至12小时。组胺还诱导了A549和NCI-H292细胞中TLR3蛋白的表达。组胺和聚肌苷酸-聚胞苷酸（poly (I:C)），一种特异性TLR3配体，刺激了两种细胞类型中白细胞介素（IL）-8的分泌。此外，组胺增强了poly (I:C)诱导的两种细胞类型中IL-8的分泌和核因子κB（NF-κB）的磷酸化，且组胺H1受体拮抗剂抑制了组胺的作用。总之，组胺选择性地上调TLR3的表达，并刺激细胞分泌IL-8。组胺还增强了poly (I:C)诱导的IL-8分泌和NF-κB的磷酸化。这些观察结果表明，组胺可能在增强气道对病毒感染的天然免疫反应中起重要作用。
