Cargando…

Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling

PURPOSE: Dry eye condition is an extrahepatic manifestation associated with chronic hepatitis C virus (HCV) infection. Since conjunctival inflammation can contribute to the dry eye condition, in the present study we analyzed the conjunctival inflammatory response to HCV core and NS3 proteins. METHOD...

Descripción completa

Detalles Bibliográficos
Autores principales: Rajalakshmy, Ayilam Ramachandran, Malathi, Jambulingam, Madhavan, Hajib Naraharirao, Srinivasan, Bhaskar, Iyer, Geetha Krishnan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173667/
https://www.ncbi.nlm.nih.gov/pubmed/25352745
_version_ 1782336244896759808
author Rajalakshmy, Ayilam Ramachandran
Malathi, Jambulingam
Madhavan, Hajib Naraharirao
Srinivasan, Bhaskar
Iyer, Geetha Krishnan
author_facet Rajalakshmy, Ayilam Ramachandran
Malathi, Jambulingam
Madhavan, Hajib Naraharirao
Srinivasan, Bhaskar
Iyer, Geetha Krishnan
author_sort Rajalakshmy, Ayilam Ramachandran
collection PubMed
description PURPOSE: Dry eye condition is an extrahepatic manifestation associated with chronic hepatitis C virus (HCV) infection. Since conjunctival inflammation can contribute to the dry eye condition, in the present study we analyzed the conjunctival inflammatory response to HCV core and NS3 proteins. METHODS: We used primary human conjunctival fibroblasts for our study. Cytokines were measured with enzyme-linked immunosorbent assay (ELISA). Toll-like receptor (TLR) and cell adhesion molecule gene expression patterns were analyzed with semiquantitative reverse transcription (RT)–PCR. Immunofluorescence staining was performed for the MyD88, nuclear factor-kappa B (NF-kB), and inducible nitric oxide synthase (iNOS) proteins. Nitric oxide (NO) was measured with the Griess assay; terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed for apoptosis and cell viability, respectively. RESULTS: When exposed to the HCV core and NS3 proteins, the conjunctival fibroblasts secreted interleukin-8 (IL-8), IL-6, tumor necrosis factor-alpha (TNF-α), and IL-10 in a dose-dependent manner. Various TLRs were involved in the innate immune response via MyD88 signaling without NF-kB involvement. The gene expression of cell adhesion molecules such as CD44 and ICAM-1 was upregulated, and the cells secreted NO via iNOS. As the sum of these stress responses, the cells underwent apoptosis, which eventually lead to cell death. CONCLUSIONS: HCV core and NS3 proteins induced conjunctival inflammation that may form the pathogenesis of dry eye condition.
format Online
Article
Text
id pubmed-4173667
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Molecular Vision
record_format MEDLINE/PubMed
spelling pubmed-41736672014-10-28 Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling Rajalakshmy, Ayilam Ramachandran Malathi, Jambulingam Madhavan, Hajib Naraharirao Srinivasan, Bhaskar Iyer, Geetha Krishnan Mol Vis Research Article PURPOSE: Dry eye condition is an extrahepatic manifestation associated with chronic hepatitis C virus (HCV) infection. Since conjunctival inflammation can contribute to the dry eye condition, in the present study we analyzed the conjunctival inflammatory response to HCV core and NS3 proteins. METHODS: We used primary human conjunctival fibroblasts for our study. Cytokines were measured with enzyme-linked immunosorbent assay (ELISA). Toll-like receptor (TLR) and cell adhesion molecule gene expression patterns were analyzed with semiquantitative reverse transcription (RT)–PCR. Immunofluorescence staining was performed for the MyD88, nuclear factor-kappa B (NF-kB), and inducible nitric oxide synthase (iNOS) proteins. Nitric oxide (NO) was measured with the Griess assay; terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed for apoptosis and cell viability, respectively. RESULTS: When exposed to the HCV core and NS3 proteins, the conjunctival fibroblasts secreted interleukin-8 (IL-8), IL-6, tumor necrosis factor-alpha (TNF-α), and IL-10 in a dose-dependent manner. Various TLRs were involved in the innate immune response via MyD88 signaling without NF-kB involvement. The gene expression of cell adhesion molecules such as CD44 and ICAM-1 was upregulated, and the cells secreted NO via iNOS. As the sum of these stress responses, the cells underwent apoptosis, which eventually lead to cell death. CONCLUSIONS: HCV core and NS3 proteins induced conjunctival inflammation that may form the pathogenesis of dry eye condition. Molecular Vision 2014-09-25 /pmc/articles/PMC4173667/ /pubmed/25352745 Text en Copyright © 2014 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Rajalakshmy, Ayilam Ramachandran
Malathi, Jambulingam
Madhavan, Hajib Naraharirao
Srinivasan, Bhaskar
Iyer, Geetha Krishnan
Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling
title Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling
title_full Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling
title_fullStr Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling
title_full_unstemmed Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling
title_short Hepatitis C virus core and NS3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling
title_sort hepatitis c virus core and ns3 antigens induced conjunctival inflammation via toll-like receptor–mediated signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173667/
https://www.ncbi.nlm.nih.gov/pubmed/25352745
work_keys_str_mv AT rajalakshmyayilamramachandran hepatitiscviruscoreandns3antigensinducedconjunctivalinflammationviatolllikereceptormediatedsignaling
AT malathijambulingam hepatitiscviruscoreandns3antigensinducedconjunctivalinflammationviatolllikereceptormediatedsignaling
AT madhavanhajibnaraharirao hepatitiscviruscoreandns3antigensinducedconjunctivalinflammationviatolllikereceptormediatedsignaling
AT srinivasanbhaskar hepatitiscviruscoreandns3antigensinducedconjunctivalinflammationviatolllikereceptormediatedsignaling
AT iyergeethakrishnan hepatitiscviruscoreandns3antigensinducedconjunctivalinflammationviatolllikereceptormediatedsignaling