Mite allergen Der-p2 triggers human B lymphocyte activation and Toll-like receptor-4 induction
Journal
PLoS ONE
Journal Volume
6
Journal Issue
9
Date Issued
2011
Author(s)
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. Methodology/Principal Findings: 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/Significance: 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. ? 2011 Tsai et al.
SDGs
Other Subjects
2 (2 amino 3 methoxyphenyl)chromone; dexamethasone; house dust allergen; immunoglobulin enhancer binding protein; mite allergen Der p2; mitogen activated protein kinase; mitogen activated protein kinase inhibitor; mitogen activated protein kinase p38; mitogen activated protein kinase phosphatase 1; neutralizing antibody; protein MD 2; small interfering RNA; toll like receptor 4; unclassified drug; autacoid; cytokine; Derp2 allergen, Dermatophagoides pteronyssinus; dexamethasone; DUSP1 protein, human; immunoglobulin enhancer binding protein; LY96 protein, human; mitogen activated protein kinase; mitogen activated protein kinase p38; mitogen activated protein kinase phosphatase 1; TLR4 protein, human; toll like receptor 4; allergic disease; article; B lymphocyte activation; cytokine response; dephosphorylation; down regulation; enzyme phosphorylation; gene expression regulation; human; human cell; immune response; lymphocyte proliferation; protein expression; protein function; protein induction; signal transduction; upregulation; animal; B lymphocyte; biological model; cell line; cell proliferation; cytology; Dermatophagoides pteronyssinus; drug effect; enzymology; immunology; lymphocyte activation; metabolism; mite; mouse; phosphorylation; Acari; Pyroglyphidae; Animals; Antigens, Dermatophagoides; B-Lymphocytes; Cell Line; Cell Proliferation; Cytokines; Dermatophagoides pteronyssinus; Dexamethasone; Dual Specificity Phosphatase 1; Extracellular Signal-Regulated MAP Kinases; Humans; Inflammation Mediators; Lymphocyte Activation; Lymphocyte Antigen 96; Mice; Mites; Models, Immunological; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Toll-Like Receptor 4; Up-Regulation
Type
journal article