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標題: Mite Allergen Der-p2 Triggers Human B Lymphocyte Activation and Toll-Like Receptor-4 Induction
作者: Tsai, Jaw-Ji
Liu, Shing-Hwa
Yin, Sui-Chu
Yang, Cheng-Ning
Hsu, Hong-Sheng
Chen, Wen-Bao
Liao, En-Chih
Lee, Wen-Jane
Pan, Hung-Chuan
Sheu, Meei-Ling
關鍵字: map kinase phosphatase-1;innate immune-responses;protein;tlr4;lung;mice;lipopolysaccharide;infection;mediator;cells
Project: Plos One, Volume 6, Issue 9, Page(s) e23249.
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 proinflammatory 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-kappa B 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.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0023249
Appears in Collections:生物醫學研究所

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