The early growth response factor-1 is involved in stem cell factor (SCF)-induced interleukin 13 production by mast cells, but is dispensable for SCF-dependent mast cell growth.
The stem cell factor (SCF) plays a central role in the regulation of mast cell function and growth. However, roles of transcription factors involved in these processes remain incompletely defined. The early growth response factor-1 (Egr-1) is a member of the zinc finger transcription factor family. A role for Egr-1 in SCF-induced mast cell activation and growth was investigated in mouse bone marrow-derived mast cells (BMMC). The stimulation of BMMC with SCF induced a strong expression of Egr-1 mRNA. SCF-induced Egr-1 nuclear translocation and DNA binding were demonstrated by electrophoretic mobility shift assay (EMSA) and immunofluorescence assay. SCF-induced IL-13 expression was significantly reduced at both mRNA and protein levels in Egr-1-deficient BMMC. In addition, the synergy between IgE and SCF on IL-13 and IL-4 production was reduced in Egr-1-deficient mast cells. Interestingly, Egr-1 deficiency had little effect on SCF-induced mast cell growth. SCF-induced Egr activation likely requires tyrosine phosphorylation because a tyrosine kinase inhibitor PP2 blocked SCF-induced nuclear protein binding to Egr probe as determined by EMSA. Thus, Egr-1 is required for SCF-induced IL-13 expression, but not mast cell growth. Egr-1 represents a novel mechanism for SCF-induced mast cell activation.
Li
Bo
B
Department of Microbiology, Izaak Walton Killam Health Center, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada.
Berman
Jason
J
Tang
Jin-Tian
JT
Lin
Tong-Jun
TJ
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D005786:Gene Expression Regulation; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism*
D051766:Early Growth Response Protein 1; D018793:Interleukin-13; D012333:RNA, Messenger; D019089:Stem Cell Factor; D015847:Interleukin-4