The early growth response factor-1 contributes to interleukin-13 production by mast cells in response to stem cell factor stimulation.
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.
Li
Bo
B
Department of Microbiology and Immunology, Izaak Walton Killam Health Center, Dalhousie University, Halifax, Nova Scotia, Canada.
Berman
Jason
J
Wu
Ping
P
Liu
Fang
F
Tang
Jin-Tian
JT
Lin
Tong-Jun
TJ
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002467:Cell Nucleus / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019089:Stem Cell Factor / Q000494:pharmacology*
C412373:AG 1879; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D018793:Interleukin-13; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D019089:Stem Cell Factor; D011505:Protein-Tyrosine Kinases