Resumen
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.
| Idioma original | English |
|---|---|
| Páginas (desde-hasta) | 163-171 |
| Número de páginas | 9 |
| Publicación | Journal of Immunotoxicology |
| Volumen | 5 |
| N.º | 2 |
| DOI | |
| Estado | Published - abr. 2008 |
Nota bibliográfica
Funding Information:This work was supported by a grant from German Cancer Aid (Deutsche Krebshilfe No. 70112502). Bristol Myers Squibb financially supported the NIVAHL trial and provided the DAKO PD-L1 antibody and Autostainer Link 48. Scanning and image analysis technology was supported by the Kinderkrebsinitiative Buchholz, Holm-Seppensen.
Funding Information:
Conflict-of-interest disclosures: P.J.B. reports grants from Bristol Myers Squibb (BMS) during the conduct of the study; grants from Merck Sharp & Dohme (MSD) and Affimed Therapeutics; and grants, personal fees, and nonfinancial support from BMS and Takeda outside of the submitted work. U.K. reports personal fees and travel support, support in an advisory role, and speaker’s honoraria from BMS during the conduct of the study, as well as personal fees from BMS outside of the submitted work. A.Z reports personal fees and nonfinancial support from Takeda and nonfinancial support from Pfizer, Novartis, Gilead Sciences, Roche, BMS, Astellas, and MSD outside of the submitted work. M.F. reports grants from BMS during the conduct of the study and personal fees from Takeda, Amgen, Celgene, and BMS outside of the submitted work. B.v.T. reports grants and nonfinancial support from BMS during the conduct of the study; personal fees from Amgen, Pfizer, Gilead Sciences, and Roche; grants, personal fees, and nonfinancial support from MSD and Takeda; and grants and nonfinancial support from Novartis outside of the submitted work. W.K. institutional grant support from Roche, Amgen, Takeda, and Regeneron outside of the submitted work. P.B. reports grants from BMS during the conduct of the study. A.E. reports grants and nonfinancial support from BMS during the conduct of the study and personal fees from Takeda, BMS, and MSD outside of the submitted work. The remaining authors report no competing financial interests.
ASJC Scopus Subject Areas
- Immunology
- Toxicology
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't