Myeloid ELF1-like factor is a potent activator of interleukin-8 expression in hematopoietic cells Journal Article
| Authors: | Hedvat, C. V.; Yao, J.; Sokolic, R. A.; Nimer, S. D. |
| Article Title: | Myeloid ELF1-like factor is a potent activator of interleukin-8 expression in hematopoietic cells |
| Abstract: | Myeloid ELF1-like factor (MEF), also known as ELF4, is a member of the ETS family of transcription factors which is expressed in hematopoietic cells. MEF-deficient mice have defects in natural killer cell and natural killer T cell development, suggesting a role for MEF in regulating innate immunity. MEF also functions in myeloid cells, where it can transactivate target genes. To identify MEF target genes in a "myeloid" environment, we created an inducible expression system and used oligonucleotide microarrays to examine the transcript profile of HEL cells after induction of MEF expression. Sixteen genes were reproducibly turned on or off more than 2-fold, 8 h after induction of MEF expression, and we examined one of the genes, interleukin-8 (IL-8), in greater detail. IL-8 is a CXC chemokine involved in neutrophil chemoattraction, angiogenesis, and stem cell mobilization. It is expressed by several tumor types, and its expression is regulated primarily transcriptionally. The IL-8 promoter contains three ETS binding sites, and we identified the specific site that binds MEF and is required for MEF responsiveness. MEF, but not the closely related ETS factors PEA3, ETS1, ETS2, ELF1, or PU.1, strongly activates the IL-8 promoter. MEF overexpression is sufficient to induce IL-8 protein expression, and reduction in MEF expression (using RNA interference) results in decreased IL-8 levels. These data demonstrates that MEF is an important regulator of IL-8 expression. |
| Keywords: | unclassified drug; promoter region; dna-binding proteins; nonhuman; protein domain; reproducibility; proteins; animal cell; animals; gene targeting; genes; interleukin 8; protein binding; rna, small interfering; rna interference; angiogenesis; cos cells; time factors; animalia; transcription factors; gene expression regulation; immunology; transcription regulation; interleukin-8; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; nucleotide sequence; transactivation; hematopoietic cell; hematopoietic stem cells; reporter gene; natural killer cell; plasmids; neutrophils; genes, reporter; gene induction; protein family; luciferases; biochemistry; t lymphocyte activation; dna, complementary; enzyme active site; cells; promoter regions (genetics); transcription factor elf 1; humans; priority journal; article; killer cells; transcription factor elf 4; transcription factor ets 1 |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 279 |
| Issue: | 8 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2004-02-20 |
| Start Page: | 6395 |
| End Page: | 6400 |
| Language: | English |
| DOI: | 10.1074/jbc.M307524200 |
| PROVIDER: | scopus |
| PUBMED: | 14625302 |
| DOI/URL: | |
| Notes: | J. Biol. Chem. -- Cited By (since 1996):26 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Molecular Sequence Numbers: GENBANK: D16583, J03910, M14758, M53751, M57731, S68271, U09578, U18062, U28833, U35451, U65579, X06182, Y00339, Y00787, Z48973; -- Source: Scopus |
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