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Publication : 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.

First Author  Li B Year  2006
Journal  Blood Volume  107
Issue  7 Pages  2814-20
PubMed ID  16317093 Mgi Jnum  J:131243
Mgi Id  MGI:3773390 Doi  10.1182/blood-2005-09-3610
Citation  Li B, et al. (2006) 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 107(7):2814-20
abstractText  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.
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