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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2814-2820. Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-09-3610.
IMMUNOBIOLOGY 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 stimulationFrom the Department of Microbiology and Immunology and the Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
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 marrowderived 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-1deficient (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 Fc
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