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Expression and potential role of major inflammatory cytokines in experimental keratomycosis
PURPOSE: The aim of this study was to investigate the expression and regulation of the four major inflammatory cytokines in fungal keratitis (FK) with the goal of further understanding its pathogenesis in order to develop more effective therapeutic approaches. METHODS: Aspergillus fumigatus and Cand...
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Formato: | Texto |
Lenguaje: | English |
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Molecular Vision
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707360/ https://www.ncbi.nlm.nih.gov/pubmed/19590756 |
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author | Zhong, Wenxian Yin, Hongmei Xie, Lixin |
author_facet | Zhong, Wenxian Yin, Hongmei Xie, Lixin |
author_sort | Zhong, Wenxian |
collection | PubMed |
description | PURPOSE: The aim of this study was to investigate the expression and regulation of the four major inflammatory cytokines in fungal keratitis (FK) with the goal of further understanding its pathogenesis in order to develop more effective therapeutic approaches. METHODS: Aspergillus fumigatus and Candida albicans were the corneal pathogens selected for this study to establish murine FK using epikeratophakia with the aid of corneal epithelium erasion. One, three, five, and seven days post-infection, the corneal lesions and inflammatory responses were observed by slit-lamp and histopathology, and the expressions of the four inflammatory cytokines, macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant (KC), interleukin-1β (IL-1β), and interleukin-6 (IL-6), in the infected corneas were determined using reverse transcription polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA). For the intervention experiment with neutralizing antibodies, the experimental mice were then injected subconjunctivally with 5 μl (2 ng/μl) MIP-2 or IL-1β polyclonal antibody 1 h before and 24 h after surgery. Reestablishment of the FK murine model was performed following injection. Effects of MIP-2 or IL-1β polyclonal antibody on the corneal diseases were observed by slit-lamp microscopy, histopathology, and ELISA. RESULTS: Expression of MIP-2, KC, IL-1β, and IL-6 was upregulated significantly in the infected group one, three, five, and seven days after surgery. Following treatment with an MIP-2 polyclonal antibody, the corneal clinical scores and inflammatory responses decreased, the MIP-2 protein levels were downregulated significantly (p<0.01), and the KC protein levels decreased slightly (p>0.05). Upon administration of IL-1β polyclonal antibodies, the decrease in clinical scores, inflammatory responses, and protein levels of MIP-2 and KC was apparent at 1 and 3 days after infection (p<0.01). CONCLUSIONS: A persistent, high level expression of MIP-2 and IL-1β is an important and even major factor in the corneal pathogenesis of FK. Specific polyclonal neutralizing antibodies may be administered to inhibit the major chemokines and cytokines responsible for corneal damage thus effectively relieving the injury caused by FK. |
format | Text |
id | pubmed-2707360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Molecular Vision |
record_format | MEDLINE/PubMed |
spelling | pubmed-27073602009-07-09 Expression and potential role of major inflammatory cytokines in experimental keratomycosis Zhong, Wenxian Yin, Hongmei Xie, Lixin Mol Vis Research Article PURPOSE: The aim of this study was to investigate the expression and regulation of the four major inflammatory cytokines in fungal keratitis (FK) with the goal of further understanding its pathogenesis in order to develop more effective therapeutic approaches. METHODS: Aspergillus fumigatus and Candida albicans were the corneal pathogens selected for this study to establish murine FK using epikeratophakia with the aid of corneal epithelium erasion. One, three, five, and seven days post-infection, the corneal lesions and inflammatory responses were observed by slit-lamp and histopathology, and the expressions of the four inflammatory cytokines, macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant (KC), interleukin-1β (IL-1β), and interleukin-6 (IL-6), in the infected corneas were determined using reverse transcription polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA). For the intervention experiment with neutralizing antibodies, the experimental mice were then injected subconjunctivally with 5 μl (2 ng/μl) MIP-2 or IL-1β polyclonal antibody 1 h before and 24 h after surgery. Reestablishment of the FK murine model was performed following injection. Effects of MIP-2 or IL-1β polyclonal antibody on the corneal diseases were observed by slit-lamp microscopy, histopathology, and ELISA. RESULTS: Expression of MIP-2, KC, IL-1β, and IL-6 was upregulated significantly in the infected group one, three, five, and seven days after surgery. Following treatment with an MIP-2 polyclonal antibody, the corneal clinical scores and inflammatory responses decreased, the MIP-2 protein levels were downregulated significantly (p<0.01), and the KC protein levels decreased slightly (p>0.05). Upon administration of IL-1β polyclonal antibodies, the decrease in clinical scores, inflammatory responses, and protein levels of MIP-2 and KC was apparent at 1 and 3 days after infection (p<0.01). CONCLUSIONS: A persistent, high level expression of MIP-2 and IL-1β is an important and even major factor in the corneal pathogenesis of FK. Specific polyclonal neutralizing antibodies may be administered to inhibit the major chemokines and cytokines responsible for corneal damage thus effectively relieving the injury caused by FK. Molecular Vision 2009-07-04 /pmc/articles/PMC2707360/ /pubmed/19590756 Text en http://creativecommons.org/licenses/by/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. |
spellingShingle | Research Article Zhong, Wenxian Yin, Hongmei Xie, Lixin Expression and potential role of major inflammatory cytokines in experimental keratomycosis |
title | Expression and potential role of major inflammatory cytokines in experimental keratomycosis |
title_full | Expression and potential role of major inflammatory cytokines in experimental keratomycosis |
title_fullStr | Expression and potential role of major inflammatory cytokines in experimental keratomycosis |
title_full_unstemmed | Expression and potential role of major inflammatory cytokines in experimental keratomycosis |
title_short | Expression and potential role of major inflammatory cytokines in experimental keratomycosis |
title_sort | expression and potential role of major inflammatory cytokines in experimental keratomycosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707360/ https://www.ncbi.nlm.nih.gov/pubmed/19590756 |
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