Mite allergen Der-p2 triggers human B lymphocyte activation and Toll-like receptor-4 induction

Autor: Wen Jane Lee, Jaw Ji Tsai, Meei-Ling Sheu, En Chih Liao, Shing-Hwa Liu, Hong Sheng Hsu, Hung Chuan Pan, Wen Bao Chen, Cheng Ning Yang, Sui Chu Yin
Jazyk: angličtina
Rok vydání: 2011
Předmět:
B Cells
Anatomy and Physiology
Lipopolysaccharide
Dermatophagoides pteronyssinus
lcsh:Medicine
Lymphocyte Activation
p38 Mitogen-Activated Protein Kinases
Biochemistry
Dexamethasone
Mice
chemistry.chemical_compound
immune system diseases
Immune Physiology
Molecular Cell Biology
Signaling in Cellular Processes
Membrane Receptor Signaling
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
lcsh:Science
Immune Response
B-Lymphocytes
Mites
Toll-like receptor
Multidisciplinary
biology
Allergy and Hypersensitivity
Mechanisms of Signal Transduction
NF-kappa B
respiratory system
Signaling Cascades
Up-Regulation
Cytokines
Medicine
Inflammation Mediators
Research Article
Signal Transduction
Lymphocyte antigen 96
Clinical Research Design
Immune Cells
Immunology
Lymphocyte Antigen 96
Microbiology
Cell Growth
Cell Line
Immune Activation
Immune system
Downregulation and upregulation
Antigen
otorhinolaryngologic diseases
Animals
Humans
Antigens
Dermatophagoides
Biology
Cell Proliferation
Inflammation
House dust mite
lcsh:R
Models
Immunological
Immunity
Dual Specificity Phosphatase 1
biology.organism_classification
respiratory tract diseases
Toll-Like Receptor 4
chemistry
Immune System
TLR4
Clinical Immunology
lcsh:Q
Zdroj: PLoS ONE, Vol 6, Iss 9, p e23249 (2011)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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