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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Vision
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173667/ https://www.ncbi.nlm.nih.gov/pubmed/25352745 |
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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 |
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