title: Enhanced Allergic Inflammation of Der p 2 Affected by Polymorphisms of MD-2 Promoter.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Translational Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.; Department of BioIndustry Technology, Da Yeh University, Changhua, Taiwan.; Department of Medical Technology, Jen Ten College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: En Chih
authors.initials: EC
authors.lastname: Liao
authors.affiliation: Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chia Wei
authors.initials: CW
authors.lastname: Hsieh
authors.affiliation: Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Ching Yun
authors.initials: CY
authors.lastname: Chang
authors.affiliation: College of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Sheng Jie
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: College of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Meei Ling
authors.initials: ML
authors.lastname: Sheu
authors.affiliation: College of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Sheng Mao
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.; College of Life Sciences, National Chung Hsing University, Taichung, Taiwan.; Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan. jawji@vghtc.gov.tw.
authors.forename: Jaw Ji
authors.initials: JJ
authors.lastname: Tsai
keywords: Der p 2; Dermatophagoides pteronyssinus; allergy; myeloid differentiation-2; single nucleotide polymorphisms