A study of RIG-I family dependent ocular surface inflammation

眼表面上皮细胞表达TLR3及其配体PolyI：C，刺激可诱导炎性细胞因子和I型干扰素的分泌。最近有报道RIG-I和MDA5也识别病毒dsRNA模拟PolyI：C。在这项研究中，我们研究了RIG-I和/或MDA5是否在结膜上皮细胞的PolyI：C诱导反应中起作用。人结膜上皮细胞也表达RIG-I、MDA-5和TLR3基因和蛋白。在PolyI：C刺激下，RIG-I和MDA-5的表达显著上调，而TLR3的表达无明显上调。我们还利用IPS-1KO和TLR3KO小鼠检测了IPS-1和TLR3在结膜上皮细胞中的功能。Cxcl10、Mx1、Ifi44、Ifi203、Iigp2和Rtp4主要受IPS-1调控，CCL5受TLR3调控，Rsad2、Mx2和Cmpk2受TLR3和IPS-1调控。结果表明，结膜上皮细胞表达RIG-I和MDA5，参与PolyI：C诱导结膜上皮细胞产生细胞因子。

Ocular surface epithelium expressed TLR3 and its ligand, polyI:C, stimulation induced the secretion of inflammatory cytokines and type I IFN. It was recently reported that RIG-I and MDA5 also recognize viral dsRNA mimicking polyI:C. In this study, we investigated whether RIG-I and/or MDA5 contribute to polyI:C-inducible responses in conjunctival epithelium. Human conjunctival epithelial cells also expressed RIG-I, MDA-5 and TLR3 mRNA and protein. The expression of RIG-I and MDA-5, but not of TLR3, was markedly up-regulated upon polyI:C stimulation. We also examined the function of IPS-1 and TLR3 in conjunctival epithelium using IPS-1 KO and TLR3 KO mice. Cxcl10, Mx1, Ifi44, Ifi203, Iigp2 and Rtp4 were dominantly regulated by IPS-1, Ccl5 by TLR3, and Rsad2, Mx2 and Cmpk2 were regulated by TLR3 and IPS-1. Our results showed that conjunctival epithelial cells express RIG-I and MDA5,which contributes to polyI:C-inducible cytokine production in conjunctival epithelial cells.