Abstract

Stem cell factor (SCF) is not only critical for mast cell development, but also an important mast cell functional regulator. However, roles of transcription factors involved in SCF-induced effects remain incompletely defined. Early growth response factor-1 (Egr-1) is a member of zinc-finger transcription factor family. Mouse bone marrow-derived mast cells (BMMC) were used to examine a role of Egr-1 in SCF-induced mast cell activation and growth. SCF induced a strong and rapid expression of Egr-1 mRNA as tested by real-time PCR analysis. SCF-induced Egr-1 nuclear translocation and DNA binding were demonstrated by electrophoretic mobility shift assay (EMSA) and immunofluorescence assay. To examine if Egr-1 is required for SCF-induced IL-13 expression, Egr-1-deficient BMMC were used. Levels of SCF-induced IL-13 mRNA and protein were reduced in Egr-1 deficient BMMC when compared with wild-type BMMC. Although Egr-1 is required for macrophage and lymphocyte development, SCF-induced mast cells growth was not affected by Egr-1 deficiency. Interestingly, SCF-induced Egr activation was blocked by a tyrosine kinase inhibitor PP2, suggesting a role of tyrosine phosphorylation in SCF-induced Egr-1 activation. Taken together, our results suggest that Egr-1 is required for SCF-induced IL-13 expression, but not mast cell growth.