Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter
Allergy, Asthma & Immunology Research
; : 497-506, 2015.
Article
em En
| WPRIM
| ID: wpr-114295
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ABSTRACT
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, epsilon heavy chain of IgE (Cepsilon), 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-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha 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-gamma 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.Palavras-chave
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Assunto principal:
Fenótipo
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Imunoglobulina E
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Imunoglobulinas
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RNA Mensageiro
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Citocinas
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Interleucina-8
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Interleucinas
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Interleucina-4
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Interleucina-6
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Fator de Necrose Tumoral alfa
Limite:
Humans
Idioma:
En
Revista:
Allergy, Asthma & Immunology Research
Ano de publicação:
2015
Tipo de documento:
Article