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 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.
Li
Bo
B
IWK Health Center, Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada, B3K 6R8.
Power
Melanie R
MR
Lin
Tong-Jun
TJ
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D016335:Zinc Fingers
D000941:Antigens; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E