Rajalakshmy Ayilam Ramachandran, Malathi Jambulingam, Madhavan Hajib Naraharirao
L & T Microbiology Research Centre, Vision Research Foundation, Sankara Nethralaya, Chennai 600 006, India; Centre for Nanotechnology and Advanced Biomaterials, SASTRA, Thanjavur, India.
L & T Microbiology Research Centre, Vision Research Foundation, Sankara Nethralaya, Chennai 600 006, India.
Exp Eye Res. 2014 Nov;128:117-28. doi: 10.1016/j.exer.2014.09.011. Epub 2014 Oct 1.
Direct association of dry eye syndrome and hepatitis C virus (HCV) infection is a well established fact. In this context, the current study examines the in vitro corneal inflammatory response with respect to HCV core and NS3 antigens. Toll like receptors (TLRs) are pattern recognition receptors which can mediate innate immune response. In the present study, corneal epithelial cells responded to HCV core and NS3 proteins by secreting pro-inflammatory cytokines IL-8, IL-6 and TNF-α via TLR1, TLR2 and TLR6 mediated innate immune response. MyD88/NF-kB signalling was involved in pro-inflammatory cytokine production. Corneal epithelium synthesised nitric oxide (NO) via iNOS during HCV core and NS3 exposure. On later stages of inflammation, cells underwent apoptosis which lead to cell death. SiRNA mediated silencing of TLR1, TLR2 and TLR6 resulted in a significant down regulation of IL-8 and NO. In conclusion, this study indicates that HCV core and NS3 proteins are capable of inducing immune response in corneal epithelium which can potentiate the pathology of HCV associated dry eye condition. Blocking specific TLR response can have therapeutic application in controlling the inflammatory response associated with this dry eye condition.
干眼症综合征与丙型肝炎病毒（HCV）感染的直接关联是一个已被充分证实的事实。在此背景下，当前研究考察了针对HCV核心抗原和NS3抗原的体外角膜炎症反应。Toll样受体（TLRs）是能够介导先天性免疫反应的模式识别受体。在本研究中，角膜上皮细胞通过经由TLR1、TLR2和TLR6介导的先天性免疫反应分泌促炎细胞因子IL-8、IL-6和TNF-α，对HCV核心蛋白和NS3蛋白产生反应。MyD88/NF-κB信号传导参与了促炎细胞因子的产生。在HCV核心蛋白和NS3蛋白存在的情况下，角膜上皮细胞通过诱导型一氧化氮合酶（iNOS）合成一氧化氮（NO）。在炎症后期，细胞发生凋亡，导致细胞死亡。RNA干扰（SiRNA）介导的TLR1、TLR2和TLR6沉默导致IL-8和NO显著下调。总之，本研究表明HCV核心蛋白和NS3蛋白能够在角膜上皮细胞中诱导免疫反应，这可能会加剧HCV相关性干眼症的病理过程。阻断特定的TLR反应在控制与此干眼症相关的炎症反应方面可能具有治疗应用价值。
