Specific and Redundant Roles for Nfat Transcription Factors in the Expression of Mast Cell-derived Cytokines.
From: Institute for Immunology, University of Mainz, Germany.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Nov 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 10
- Pages: 6667-74
- Medium: Print
- Language: English
- Citation (JAMA): Klein Matthias, Klein-Hessling Stefan, Palmetshofer Alois, et al. Specific and Redundant Roles for Nfat Transcription Factors in the Expression of Mast Cell-derived Cytokines.. J. Immunol. Nov 2006;177:6667-74
Abstract
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-alpha 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-alpha 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-alpha 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-alpha and IL-13 promoter induction in MC, irrespective of whether NFATc2 or NFATc1 or a combination of both is present.
Mesh Headings (Keywords): Animals, Cell Line, Tumor, Cells, Cultured, Cytokines, Down-Regulation, Interleukin-13, Mast Cells, Mice, Mice, Inbred BALB C, Mice, Knockout, NFATC Transcription Factors, Th2 Cells, Tumor Necrosis Factor-alpha, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 17082579
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