B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6 production in mast cells

The adaptor protein B cell lymphoma 10 (Bcl10) plays an essential role in the functions of the AgRs in T and B cells. In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we d...

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Veröffentlicht in:The Journal of immunology (1950) 2007-01, Vol.178 (1), p.49-57
Hauptverfasser: Chen, Yuhong, Pappu, Bhanu P, Zeng, Hu, Xue, Liquan, Morris, Stephan W, Lin, Xin, Wen, Renren, Wang, Demin
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container_issue 1
container_start_page 49
container_title The Journal of immunology (1950)
container_volume 178
creator Chen, Yuhong
Pappu, Bhanu P
Zeng, Hu
Xue, Liquan
Morris, Stephan W
Lin, Xin
Wen, Renren
Wang, Demin
description The adaptor protein B cell lymphoma 10 (Bcl10) plays an essential role in the functions of the AgRs in T and B cells. In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10 is essential for specific functions of FcepsilonR. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired FcepsilonR-mediated degranulation, indicated by decreased serotonin release, and impaired cytokine production, measured by release of IL-6. In addition, Bcl10-deficient mice display impaired IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bcl10-deficient mast cells have normal FcepsilonR-mediated Ca(2+) flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished FcepsilonR-mediated activation of NF-kappaB and decreased activation of AP-1. Thus, Bcl10 is essential for FcepsilonR-induced activation of AP-1, NF-kappaB, degranulation, and cytokine production in mast cells.
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In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10 is essential for specific functions of FcepsilonR. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired FcepsilonR-mediated degranulation, indicated by decreased serotonin release, and impaired cytokine production, measured by release of IL-6. In addition, Bcl10-deficient mice display impaired IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bcl10-deficient mast cells have normal FcepsilonR-mediated Ca(2+) flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished FcepsilonR-mediated activation of NF-kappaB and decreased activation of AP-1. 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In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10 is essential for specific functions of FcepsilonR. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired FcepsilonR-mediated degranulation, indicated by decreased serotonin release, and impaired cytokine production, measured by release of IL-6. In addition, Bcl10-deficient mice display impaired IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bcl10-deficient mast cells have normal FcepsilonR-mediated Ca(2+) flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished FcepsilonR-mediated activation of NF-kappaB and decreased activation of AP-1. 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subjects Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - physiology
Anaphylaxis - genetics
Anaphylaxis - immunology
Animals
Arachidonic Acid - metabolism
B-Cell CLL-Lymphoma 10 Protein
Calcium - metabolism
Cell Degranulation - genetics
Cytokines - metabolism
Immunoglobulin E - immunology
Interleukin-6 - metabolism
Mast Cells - immunology
Mice
Mice, Mutant Strains
Mitogen-Activated Protein Kinase Kinases - metabolism
NF-kappaB-Inducing Kinase
Phosphatidylinositol 3-Kinases - metabolism
Protein Kinase C - metabolism
Protein Serine-Threonine Kinases - metabolism
Receptors, IgE - metabolism
Serotonin - metabolism
Transcription Factor AP-1 - metabolism
title B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6 production in mast cells
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