Cytokine and Chemokine Secretion Induced by Poly(I:C) through NF-κB and Phosphoinositide 3-Kinase Signaling Pathways in Human Corneal Fibroblasts
Cytokine and Chemokine Secretion Induced by Poly(I:C) through NF-κB and Phosphoinositide 3-Kinase Signaling Pathways in Human Corneal Fibroblasts
复制标题
DOI：
10.3109/02713683.2012.721044
复制
发表时间：
2013-01
影响因子：
2
通讯作者：
T. Orita;K. Kimura;T. Nishida;K. Sonoda
中科院分区：
文献类型：
--
作者：
T. Orita;K. Kimura;T. Nishida;K. Sonoda
目的/目标：角膜病毒感染可导致炎症和瘢痕形成，最终导致失明。多聚肌苷酸-多聚胞苷酸[poly（I：C）]是一种病毒双链RNA的类似物，可诱导培养的角膜成纤维细胞分泌细胞因子和趋化因子。我们现在已经研究了核因子（NF）-κB和磷酸肌醇3-激酶（PI 3 K）信号通路在poly（I：C）诱导的角膜成纤维细胞分泌细胞因子和趋化因子中的作用。材料与方法：在不存在或存在IKK-2抑制剂或LY 294002的情况下，用poly（I：C）培养人角膜成纤维细胞，IKK-2抑制剂或LY 294002分别是NF-κB和PI 3 K信号传导的抑制剂。促炎细胞因子白细胞介素（IL）-6和趋化因子IL-8，IP-10和RANTES从细胞的释放用酶联免疫吸附测定法测量。结果：Poly（I：C）诱导角膜成纤维细胞分泌IL-6、IL-8、IP-10和RANTES。而poly（I：C）诱导的IL-6、IP-10和RANTES的分泌被IKK-2抑制剂和LY 294002抑制，IL-8的分泌仅被IKK-2抑制剂阻断。结论：poly（I：C）诱导的人角膜成纤维细胞分泌IL-6、IP-10和RANTES由NF-κB和PI 3 K信号通路介导，而IL-8由NF-κB通路介导。因此，这些信号传导途径可能有助于由病毒感染诱导的角膜基质中的局部炎症。
Purpose/Aim: Viral infection of the cornea can result in inflammation and scarring and eventually lead to blindness. Polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, induces the secretion of cytokines and chemokines from cultured corneal fibroblasts. We have now investigated the role of nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K) signaling pathways in poly(I:C)-induced cytokine and chemokine secretion from corneal fibroblasts. Materials and Methods: Human corneal fibroblasts were cultured with poly(I:C) in the absence or presence of IKK-2 inhibitor or LY294002, which are inhibitors of NF-κB and PI3K signaling, respectively. The release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokines IL-8, IP-10, and RANTES from the cells was measured with an enzyme-linked immunosorbent assay. Results: Poly(I:C) induced the secretion of IL-6, IL-8, IP-10, and RANTES from corneal fibroblasts. Whereas the poly(I:C)-induced secretion of IL-6, IP-10, and RANTES was inhibited by both IKK-2 inhibitor and LY294002, that of IL-8 was blocked only by IKK-2 inhibitor. Conclusions: The poly(I:C)-induced secretion of IL-6, IP-10, and RANTES from human corneal fibroblasts is mediated by both NF-κB and PI3K signaling pathways, whereas that of IL-8 is mediated by the NF-κB pathway. These signaling pathways thus likely contribute to local inflammation in the corneal stroma induced by viral infection.