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Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter
PURPOSE: Myeloid differentiation-2 (MD-2) has been associated with endotoxin and inflammatory disorders because it can recognize lipopolysaccharide (LPS) binding and attenuate Toll-like receptor 4 (TLR4)-mediated signaling. However, its role in allergic inflammation has yet to be clarified. We exami...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509663/ https://www.ncbi.nlm.nih.gov/pubmed/26122509 http://dx.doi.org/10.4168/aair.2015.7.5.497 |
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author | Liao, En-Chih Hsieh, Chia-Wei Chang, Ching-Yun Yu, Sheng-Jie Sheu, Meei-Ling Wu, Sheng-Mao Tsai, Jaw-Ji |
author_facet | Liao, En-Chih Hsieh, Chia-Wei Chang, Ching-Yun Yu, Sheng-Jie Sheu, Meei-Ling Wu, Sheng-Mao Tsai, Jaw-Ji |
author_sort | Liao, En-Chih |
collection | PubMed |
description | PURPOSE: Myeloid differentiation-2 (MD-2) has been associated with endotoxin and inflammatory disorders because it can recognize lipopolysaccharide (LPS) binding and attenuate Toll-like receptor 4 (TLR4)-mediated signaling. However, its role in allergic inflammation has yet to be clarified. We examined whether single nucleotide polymorphisms (SNPs) in MD-2 promoter can affect MD-2 expression and aimed to clarify the relationship between Der p 2 allergy and SNPs of MD-2 promoter. METHODS: The function of SNPs of MD-2 promoter and the effects of cytokines and immunoglobulin on the secretion and mRNA expression were investigated in 73 allergic subjects with different MD-2 gene promoter variants. Peripheral blood mononuclear cells were cultured with or without LPS in the presence of Dermatophagoides pteronyssinus group 2 allergen (Der p 2), followed by mRNA extraction and cytokine expression analysis. The culture supernatants were collected for cytokine measurement. RESULTS: Patients with the MD-2 promoter SNPs (rs1809441/rs1809442) had increased mRNA expressions of MD-2, ε heavy chain of IgE (Cε), and interleukin (IL)-8; however, only MD-2 and IL-8 were further up-regulated after Der p 2 stimulation. Patients with SNPs of MD-2 promoter tended to have high levels of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α after Der p 2 and LPS stimulation. Increased secretions of IL-6, IL-8, and IL-10 were found to be up-regulated by Der p 2 stimulation, and an increased secretion of IFN-γ and decreased secretion of IL-4 were noted after LPS stimulation. CONCLUSIONS: The high levels of proinflammatory cytokines secreted by Der p 2 were predetermined by MD-2 promoter SNPs (rs1809441/rs1809442). Through cytokine secretion by Der p 2 and LPS, these SNPs may serve as an indicator of the pathological phenotype of Der p 2-induced allergic inflammation. |
format | Online Article Text |
id | pubmed-4509663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease |
record_format | MEDLINE/PubMed |
spelling | pubmed-45096632015-09-01 Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter Liao, En-Chih Hsieh, Chia-Wei Chang, Ching-Yun Yu, Sheng-Jie Sheu, Meei-Ling Wu, Sheng-Mao Tsai, Jaw-Ji Allergy Asthma Immunol Res Original Article PURPOSE: Myeloid differentiation-2 (MD-2) has been associated with endotoxin and inflammatory disorders because it can recognize lipopolysaccharide (LPS) binding and attenuate Toll-like receptor 4 (TLR4)-mediated signaling. However, its role in allergic inflammation has yet to be clarified. We examined whether single nucleotide polymorphisms (SNPs) in MD-2 promoter can affect MD-2 expression and aimed to clarify the relationship between Der p 2 allergy and SNPs of MD-2 promoter. METHODS: The function of SNPs of MD-2 promoter and the effects of cytokines and immunoglobulin on the secretion and mRNA expression were investigated in 73 allergic subjects with different MD-2 gene promoter variants. Peripheral blood mononuclear cells were cultured with or without LPS in the presence of Dermatophagoides pteronyssinus group 2 allergen (Der p 2), followed by mRNA extraction and cytokine expression analysis. The culture supernatants were collected for cytokine measurement. RESULTS: Patients with the MD-2 promoter SNPs (rs1809441/rs1809442) had increased mRNA expressions of MD-2, ε heavy chain of IgE (Cε), and interleukin (IL)-8; however, only MD-2 and IL-8 were further up-regulated after Der p 2 stimulation. Patients with SNPs of MD-2 promoter tended to have high levels of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α after Der p 2 and LPS stimulation. Increased secretions of IL-6, IL-8, and IL-10 were found to be up-regulated by Der p 2 stimulation, and an increased secretion of IFN-γ and decreased secretion of IL-4 were noted after LPS stimulation. CONCLUSIONS: The high levels of proinflammatory cytokines secreted by Der p 2 were predetermined by MD-2 promoter SNPs (rs1809441/rs1809442). Through cytokine secretion by Der p 2 and LPS, these SNPs may serve as an indicator of the pathological phenotype of Der p 2-induced allergic inflammation. The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2015-09 2015-05-26 /pmc/articles/PMC4509663/ /pubmed/26122509 http://dx.doi.org/10.4168/aair.2015.7.5.497 Text en Copyright © 2015 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Liao, En-Chih Hsieh, Chia-Wei Chang, Ching-Yun Yu, Sheng-Jie Sheu, Meei-Ling Wu, Sheng-Mao Tsai, Jaw-Ji Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter |
title | Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter |
title_full | Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter |
title_fullStr | Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter |
title_full_unstemmed | Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter |
title_short | Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter |
title_sort | enhanced allergic inflammation of der p 2 affected by polymorphisms of md-2 promoter |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509663/ https://www.ncbi.nlm.nih.gov/pubmed/26122509 http://dx.doi.org/10.4168/aair.2015.7.5.497 |
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