title: Mite allergen Der-p2 triggers human B lymphocyte activation and Toll-like receptor-4 induction.
abstract: BACKGROUND
  Allergic disease can be characterized as manifestations of an exaggerated inflammatory response to environmental allergens triggers. Mite allergen Der-p2 is one of the major allergens of the house dust mite, which contributes to TLR4 expression and function in B cells in allergic patients. However, the precise mechanisms of Der-p2 on B cells remain obscure.
  
  
  RESULTS
  We investigated the effects of Der-p2 on proinflammatory cytokines responses and Toll-like receptor-4 (TLR4)-related signaling in human B cells activation. We demonstrated that Der-p2 activates pro-inflammatory cytokines, TLR4 and its co-receptor MD2. ERK inhibitor PD98059 significantly enhanced TLR4/MD2 expression in Der-p2-treated B cells. Der-p2 markedly activated mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) and decreased p38 phosphorylation in B cells. MKP-1-siRNA downregulated TLR4/MD2 expression in Der-p2-treated B cells. In addition, Der-p2 significantly up-regulated expression of co-stimulatory molecules and increased B cell proliferation. Neutralizing Der-p2 antibody could effectively abrogate the Der-p2-induced B cell proliferation. Der-p2 could also markedly induce NF-κB activation in B cells, which could be counteracted by dexamethasone.
  
  
  CONCLUSIONS
  These results strongly suggest that Der-p2 is capable of triggering B cell activation and MKP-1-activated p38/MAPK dephosphorylation-regulated TLR4 induction, which subsequently enhances host immune, defense responses and development of effective allergic disease therapeutics in B cells.
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors: Jaw Ji
authors: JJ
authors: Tsai
authors: Shing Hwa
authors: SH
authors: Liu
authors: Sui Chu
authors: SC
authors: Yin
authors: Cheng Ning
authors: CN
authors: Yang
authors: Hong Sheng
authors: HS
authors: Hsu
authors: Wen Bao
authors: WB
authors: Chen
authors: En Chih
authors: EC
authors: Liao
authors: Wen Jane
authors: WJ
authors: Lee
authors: Hung Chuan
authors: HC
authors: Pan
authors: Meei Ling
authors: ML
authors: Sheu
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000187:drug effects / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051218:Lymphocyte Antigen 96 / Q000378:metabolism; D051379:Mice; D008925:Mites / Q000276:immunology*; D018448:Models, Immunological; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; C559662:Derp2 allergen, Dermatophagoides pteronyssinus; D018836:Inflammation Mediators; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1