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 stimulation

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 IgEdependent 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 Fc RI signaling and is required for the full responsiveness of IgE-dependent TNF and IL-13 production by mast cells. (Blood. 2006;107:2814-2820)