Molecular Mechanisms of B Lymphocyte Activation by the Immune Response Modifier R-848
| Autor: | Gail A. Bishop, M A Tomai, Sangita V. Jalukar, Yina Hsing, Luis M. Ramirez, Bruce S. Hostager |
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| Rok vydání: | 2000 |
| Předmět: |
Transcriptional Activation
p38 mitogen-activated protein kinases Immunology Lymphocyte Activation p38 Mitogen-Activated Protein Kinases Receptors Tumor Necrosis Factor Cell Line Mice chemistry.chemical_compound Adjuvants Immunologic medicine Animals Humans Immunology and Allergy CD154 Antibody-Producing Cells Transcription factor B cell Mice Knockout B-Lymphocytes CD40 biology Interleukin-6 Tumor Necrosis Factor-alpha Kinase Imidazoles JNK Mitogen-Activated Protein Kinases NF-kappa B Proteins Cell Differentiation TNF Receptor-Associated Factor 2 Cell biology Enzyme Activation Mice Inbred C57BL Imidazoquinoline medicine.anatomical_structure chemistry biology.protein Female Tumor necrosis factor alpha Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | The Journal of Immunology. 165:5552-5557 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The imidazoquinoline R-848, originally identified as a highly effective antiviral agent, has recently been shown to be capable of potent B lymphocyte activation. The B cell-activating properties of R-848 are strikingly similar to the effects of the CD40 ligand CD154. The present study demonstrates that this similarity extends to the intracellular signaling pathways triggered by the compound, although both overlapping and distinct mechanisms of signaling were seen. Like CD40 ligation, R-848 stimulated activation of the stress-activated protein kinases c-Jun kinase and p38 and activated the NF-κB family of transcription factors. Both R-848- and CD40-mediated B cell differentiation were dependent upon NF-κB activation, although the relative importance of individual NF-κB family members appeared to differ between R-848- and CD40-mediated signals. Both signals were partially dependent upon induction of TNF-α and IL-6, and the cytoplasmic adaptor molecule TNF receptor-associated factor 2 is involved in both R-848- and CD40-mediated differentiation. |
| Databáze: | OpenAIRE |
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