De Novo Synthesis of Early Growth Response Factor-1 is Required for the Full Responsiveness of Mast Cells to Produce Tnf and Il-13 by Ige and Antigen Stimulation.
From: IWK Health Center, Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada, B3K 6R8.
Blood
- Publish Date: Apr 2006
- ISSN: 0006-4971
- Volume: 107
- Issue: 7
- Pages: 2814-20
- Medium: Print
- Language: English
- Citation (JAMA): Li Bo, Power Melanie R, Lin Tong-Jun, et al. De Novo Synthesis of Early Growth Response Factor-1 is Required for the Full Responsiveness of Mast Cells to Produce Tnf and Il-13 by Ige and Antigen Stimulation.. Blood Apr 2006;107:2814-20
Abstract
Early growth-response factor 1 (Egr-1) is a zinc-finger transcription factor that plays a regulatory role in the expression of many genes important for inflammation. Whether Egr-1 is involved in IgE-dependent mast-cell activation was investigated. We demonstrated that IgE and antigen (TNP) stimulation induced a rapid expression of Egr-1 mRNA in mouse bone marrow-derived mast cells (BMMCs). As early as 15 to 20 minutes after IgE + TNP stimulation, Egr-1 protein was detectable in the nucleus of BMMCs by immunofluorescence or electrophoretic mobility shift assay. To examine a role for Egr-1 in IgE-dependent cytokine production by mast cells, Egr-1-deficient (Egr-1-/-) BMMCs were developed from the bone marrow cells of Egr-1 knockout mice. Egr-1-/- BMMCs express similar levels of surface c-kit and IgE receptor as compared with those on Egr-1+/+ BMMCs. Importantly, IgE + TNP-induced TNF and IL-13 expression was significantly reduced at both mRNA and protein levels in Egr-1-/- BMMCs as compared with those in Egr-1+/+ BMMCs. Thus, our results suggest that de novo synthesis of Egr-1 represents a novel mechanism in FcepsilonRI signaling and is required for the full responsiveness of IgE-dependent TNF and IL-13 production by mast cells.
Mesh Headings (Keywords): Animals, Antigens, Bone Marrow Cells, Cells, Cultured, Early Growth Response Protein 1, Flow Cytometry, Immunoglobulin E, Interleukin-13, Mast Cells, Mice, Mice, Inbred C57BL, Mice, Knockout, Tumor Necrosis Factor-alpha, Zinc Fingers
Check for Full Text / PubMed Unique Identifier (PMID): 16317093
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