Defective Toll-like receptor 9-mediated cytokine production in B cells from Bruton's tyrosine kinase-deficient mice
| Autor: | Maroof Hasan, Leonardo Vargas, Anna Berglöf, Gabriela Lopez-Herrera, Jessica M. Lindvall, C. I. Edvard Smith, K. Emelie M. Blomberg |
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| Rok vydání: | 2007 |
| Předmět: |
Cell Survival
medicine.medical_treatment Immunology Lymphocyte Activation Receptor tyrosine kinase Mice immune system diseases hemic and lymphatic diseases medicine Agammaglobulinaemia Tyrosine Kinase Immunology and Allergy Bruton's tyrosine kinase Animals Cells Cultured Cell Proliferation Toll-like receptor B-Lymphocytes biology Gene Expression Profiling Interleukins TLR9 Interleukin Original Articles Protein-Tyrosine Kinases Molecular biology Interleukin-10 Up-Regulation Mice Inbred C57BL Cytokine Oligodeoxyribonucleotides Toll-Like Receptor 9 ROR1 biology.protein Mice Inbred CBA Cytokines Inflammation Mediators Tyrosine kinase Spleen |
| Zdroj: | Karolinska Institutet |
| ISSN: | 1365-2567 |
| Popis: | Summary Bruton’s tyrosine kinase (Btk), a member of the Tec family of tyrosine kinases, plays an important role in the differentiation and activation of B cells. Mutations affecting Btk cause immunodeficiency in both humans and mice. In this study we set out to investigate the potential role of Btk in Toll-like receptor 9 (TLR9) activation and the production of pro-inflammatory cytokines such as interleukin (IL)-6, tumour necrosis factor (TNF)-a and IL-12p40. Our data show that Btk-deficient B cells respond more efficiently to CpG-DNA stimulation, producing significantly higher levels of pro-inflammatory cytokines but lower levels of the inhibitory cytokine IL-10. The quantitative reverse transcription– polymerase chain reaction (RT-PCR) analysis presented in this work shows that mRNA production of one of the important new members of the IL-12 family, IL-27, was significantly increased in Btk-deficient B cells after CpG-DNA stimulation. In this study, we demonstrate significant differences in CpG responsiveness between transitional 1 (T1) and T2 B cells for survival and maturation. Furthermore, TLR9 expression, measured both as protein and as mRNA, was increased in Btk-defective cells, especially after TLR9 stimulation. Collectively, these data provide evidence in support of the theory that Btk regulates both TLR9 activation and expression in mouse splenic B cells. |
| Databáze: | OpenAIRE |
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