Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter.
10.4168/aair.2015.7.5.497
- Author:
En Chih LIAO
1
;
Chia Wei HSIEH
;
Ching Yun CHANG
;
Sheng Jie YU
;
Meei Ling SHEU
;
Sheng Mao WU
;
Jaw Ji TSAI
Author Information
1. Center for Translational Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
- Publication Type:Original Article
- Keywords:
Dermatophagoides pteronyssinus;
Der p 2;
myeloid differentiation-2;
single nucleotide polymorphisms;
allergy
- MeSH:
Cytokines;
Dermatophagoides pteronyssinus;
Humans;
Hypersensitivity;
Immunoglobulin E;
Immunoglobulins;
Inflammation*;
Interleukin-10;
Interleukin-4;
Interleukin-6;
Interleukin-8;
Interleukins;
Phenotype;
Polymorphism, Single Nucleotide;
RNA, Messenger;
Toll-Like Receptor 4;
Tumor Necrosis Factor-alpha
- From:Allergy, Asthma & Immunology Research
2015;7(5):497-506
- CountryRepublic of Korea
- Language:English
-
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.
