title: HCV core and NS3 proteins mediate toll like receptor induced innate immune response in corneal epithelium.
abstract: 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.
authors.affiliation: L & T Microbiology Research Centre, Vision Research Foundation, Sankara Nethralaya, Chennai 600 006, India; Centre for Nanotechnology and Advanced Biomaterials, SASTRA, Thanjavur, India.
authors.forename: Ayilam Ramachandran
authors.initials: AR
authors.lastname: Rajalakshmy
authors.affiliation: L & T Microbiology Research Centre, Vision Research Foundation, Sankara Nethralaya, Chennai 600 006, India.
authors.forename: Jambulingam
authors.initials: J
authors.lastname: Malathi
authors.affiliation: L & T Microbiology Research Centre, Vision Research Foundation, Sankara Nethralaya, Chennai 600 006, India. Electronic address: drhnm@snmail.org.
authors.forename: Hajib Naraharirao
authors.initials: HN
authors.lastname: Madhavan
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000276:immunology*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D020868:Gene Silencing; D016174:Hepacivirus / Q000737:chemistry*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D060888:Real-Time Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014758:Viral Core Proteins / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000494:pharmacology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D009569:Nitric Oxide; D051193:Toll-Like Receptors; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: Cornea; Dry eye; Hepatitis C virus; Inflammation; Toll like receptors; Viral antigen