Specific and Redundant Roles for NFAT Transcription Factors in the Expression of Mast Cell-Derived Cytokines
| Autor: | Marc Becker, Michael Stassen, Stefan Klein-Hessling, Edgar Schmitt, Christine Tertilt, Valeska Heib, Edgar Serfling, Tobias Bopp, Hansjörg Schild, Matthias Klein, Christian Taube, Alois Palmetshofer |
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| Rok vydání: | 2006 |
| Předmět: |
Immunology
Down-Regulation Immunoglobulin E Mice chemistry.chemical_compound Th2 Cells Cell Line Tumor medicine Animals Immunology and Allergy Mast Cells Transcription factor Cells Cultured Mice Knockout Mice Inbred BALB C Gene knockdown Interleukin-13 Innate immune system NFATC Transcription Factors biology Tumor Necrosis Factor-alpha Degranulation NFAT Mast cell Up-Regulation Cell biology medicine.anatomical_structure chemistry Ionomycin biology.protein Cytokines |
| Zdroj: | The Journal of Immunology. 177:6667-6674 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | By virtue of their ability to express a plethora of biologically highly active mediators, mast cells (MC) are involved in both adaptive and innate immune responses. MC-derived Th2-type cytokines are thought to act as local amplifiers of Th2 reactions, including chronic inflammatory disorders such as allergic asthma, whereas MC-derived TNF-α is a critical initiator of antimicrobial defense. In this study, we demonstrate that the transcription factors NFATc1 and NFATc2 are part of a MC-specific signaling network that regulates the expression of TNF-α and IL-13, whereas NFATc3 is dispensable. Primary murine bone marrow-derived MC from NFATc2−/− mice, activated by either ionomycin or IgE/Ag cross-link, display a strong reduction in the production of these cytokines, compared with bone marrow-derived MC from wild-type mice. Detailed analyses of TNF-α and IL-13 expression using small interfering RNA-mediated knockdown reveals that both NFATc2 and NFATc1 are able to drive the expression of these cytokines, whereas neither degranulation nor the expression of IL-6 depends on NFAT activity. These results support the view that high NFAT activity is necessary for TNF-α and IL-13 promoter induction in MC, irrespective of whether NFATc2 or NFATc1 or a combination of both is present. |
| Databáze: | OpenAIRE |
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