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-κB 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- κB 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-κB, c-Jun and Sp1 can functionally cooperate to elicit maximal activation of the promoter.
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
Received 6 September 2004; received after revision 25 October 2004; accepted 12 November 2004
Rights and permissions
About this article
Cite this article
Lee, K.W., Lee, Y., Kwon, H.J. et al. Sp1-associated activation of macrophage inflammatory protein-2 promoter by CpG-oligodeoxynucleotide and lipopolysaccharide. CMLS, Cell. Mol. Life Sci. 62, 188–198 (2005). https://doi.org/10.1007/s00018-004-4399-y
Issue Date:
DOI: https://doi.org/10.1007/s00018-004-4399-y