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Sp1-associated activation of macrophage inflammatory protein-2 promoter by CpG-oligodeoxynucleotide and lipopolysaccharide.

Authors :
Lee, K.-W.
Lee, Y.
Kwon, H.-J.
Kim, D.-S.
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]

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