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Sp1-associated activation of macrophage inflammatory protein-2 promoter by CpG-oligodeoxynucleotide and lipopolysaccharide.
- Source :
- Cellular & Molecular Life Sciences; Jan2005, Vol. 62 Issue 2, p188-198, 11p, 2 Diagrams, 6 Graphs
- Publication Year :
- 2005
-
Abstract
- Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that is important in recruiting neutrophils to inflammatory sites. Our previous reports demonstrated that lipopolysaccharide (LPS) or CpG-oligode-oxynucleotide (CpG-ODN) rapidly induce MIP-2 gene expression in the macrophage cell line, RAW 264.7. Here, we show that the DNA sequence of the MIP-2 promoter between -114 and +14 is sufficient for strong promoter activity in LPS- or CpG-ODN-stimulated RAW 264.7 cells. Importantly, comprehensive mutant analysis reveals that an Sp1 element in the promoter region between -114 and -94 is essential for synergistic MIP-2 promoter activation by NF-?B and c-Jun regardless of the presence of an AP-1 site. By combining deletion or site-specific mutant analysis with immunocomplex assays, we also confirmed that Sp1 mediates the recruitment of transcription factors NF- ?B and c-Jun in LPS- or CpG-ODN-treated RAW 264.7 cells. Several lines of experimental evidence imply that the Sp1-binding element is an important determinant of MIP-2 promoter activity, and that NF-?B, c-Jun and Sp1 can functionally cooperate to elicit maximal activation of the promoter. [ABSTRACT FROM AUTHOR]
- Subjects :
- NUCLEOTIDE sequence
MACROPHAGES
GENE expression
IMMUNOASSAY
TRANSCRIPTION factors
Subjects
Details
- Language :
- English
- ISSN :
- 1420682X
- Volume :
- 62
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Cellular & Molecular Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 15791980
- Full Text :
- https://doi.org/10.1007/s00018-004-4399-y