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Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells

PURPOSE: Toll-like receptor 4 (TLR4), a member of the TLR family, is an important pattern recognition molecule that plays a role in the host’s innate immune responses to lipopolysaccharide (LPS), a component of gram-negative bacteria. Contact lens wear is one of the risk factors for bacterial kerati...

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Autores principales: Hara, Yuko, Shiraishi, Atsushi, Ohashi, Yuichi
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787305/
https://www.ncbi.nlm.nih.gov/pubmed/19960069
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author Hara, Yuko
Shiraishi, Atsushi
Ohashi, Yuichi
author_facet Hara, Yuko
Shiraishi, Atsushi
Ohashi, Yuichi
author_sort Hara, Yuko
collection PubMed
description PURPOSE: Toll-like receptor 4 (TLR4), a member of the TLR family, is an important pattern recognition molecule that plays a role in the host’s innate immune responses to lipopolysaccharide (LPS), a component of gram-negative bacteria. Contact lens wear is one of the risk factors for bacterial keratitis. The purpose of this study was to determine whether hypoxia or contact lens wear alters the TLR4 signaling pathways in human corneal epithelial cells (HCECs). METHOD: A simian virus 40-immortalized human corneal epithelial cell (SV40-HCEC) line was cultured under 20% O(2) or 2% O(2) and exposed to LPS. The expression of TLR4, interleukin-6 (IL-6), and IL-8 was determined using a real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. Immunoblotting was also used to determine whether the nuclear factor kappa B (NFκB) was activated in the SV40-HCEs. HCECs were obtained from 17 healthy volunteers and 18 hydrogel soft contact lens (SCL) wearers using impression cytology (IC), and the expression of the mRNA of TLR4 was determined using real-time RT-PCR. RESULTS: A reduction in the expression of the mRNA and protein of TLR4 was detected in SV40-HCECs cultured under hypoxic conditions. Hypoxia also attenuated both the LPS-induced expression of IL-6 and IL-8, and the activation of NFκB in SV40-HCECs. The expression of the mRNA of TLR4 was down-regulated in the HCECs of soft contact lens wearers. CONCLUSIONS: These results indicate that hypoxia attenuates the TLR4 signaling pathway in HCECs, suggesting that the increase in the susceptibility to bacterial infections under hypoxic conditions may be related to the TLR4 signaling pathways.
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spelling pubmed-27873052009-12-03 Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells Hara, Yuko Shiraishi, Atsushi Ohashi, Yuichi Mol Vis Research Article PURPOSE: Toll-like receptor 4 (TLR4), a member of the TLR family, is an important pattern recognition molecule that plays a role in the host’s innate immune responses to lipopolysaccharide (LPS), a component of gram-negative bacteria. Contact lens wear is one of the risk factors for bacterial keratitis. The purpose of this study was to determine whether hypoxia or contact lens wear alters the TLR4 signaling pathways in human corneal epithelial cells (HCECs). METHOD: A simian virus 40-immortalized human corneal epithelial cell (SV40-HCEC) line was cultured under 20% O(2) or 2% O(2) and exposed to LPS. The expression of TLR4, interleukin-6 (IL-6), and IL-8 was determined using a real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. Immunoblotting was also used to determine whether the nuclear factor kappa B (NFκB) was activated in the SV40-HCEs. HCECs were obtained from 17 healthy volunteers and 18 hydrogel soft contact lens (SCL) wearers using impression cytology (IC), and the expression of the mRNA of TLR4 was determined using real-time RT-PCR. RESULTS: A reduction in the expression of the mRNA and protein of TLR4 was detected in SV40-HCECs cultured under hypoxic conditions. Hypoxia also attenuated both the LPS-induced expression of IL-6 and IL-8, and the activation of NFκB in SV40-HCECs. The expression of the mRNA of TLR4 was down-regulated in the HCECs of soft contact lens wearers. CONCLUSIONS: These results indicate that hypoxia attenuates the TLR4 signaling pathway in HCECs, suggesting that the increase in the susceptibility to bacterial infections under hypoxic conditions may be related to the TLR4 signaling pathways. Molecular Vision 2009-12-02 /pmc/articles/PMC2787305/ /pubmed/19960069 Text en Copyright © 2008 Molecular Vision. 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
Hara, Yuko
Shiraishi, Atsushi
Ohashi, Yuichi
Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells
title Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells
title_full Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells
title_fullStr Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells
title_full_unstemmed Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells
title_short Hypoxia-altered signaling pathways of toll-like receptor 4 (TLR4) in human corneal epithelial cells
title_sort hypoxia-altered signaling pathways of toll-like receptor 4 (tlr4) in human corneal epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787305/
https://www.ncbi.nlm.nih.gov/pubmed/19960069
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