Regulation of macrophage inflammatory protein-2 gene expression in response to oligodeoxynucleotide containing CpG motifs in RAW 264.7 cells.
Macrophage inflammatory protein-2 (MIP-2) is a mouse C-X-C chemokine that plays an important role in the recruitment of neutrophils. The unregulated production of MIP-2 has been associated with inflammatory diseases such as arthritis, glomerulonephritis, and sepsis. We have shown that the MIP-2 gene expression is transcriptionally activated by synthetic oligodeoxynucleotide (ODN) containing unmethylated CpG dinucleotides in the context of particular base sequences (CpG-ODN) in a CpG sequence-dependent manner. Inhibition of NF-kappaB nuclear localization by coexpression of a mutant IkappaBalpha protein blocked CpG-ODN-induced transcription from a MIP-2 promoter-reporter construct, showing that NF-kappaB activation is required for MIP-2 gene expression in the CpG-ODN-signaling pathway. We also provided evidence that NF-kappaB and c-Jun contributes to the expression of MIP-2 gene in response to CpG-ODN, since ectopical expression of NF-kappaB and c-Jun in RAW 246.7 cells leads to dramatically increase the ability of CpG-ODN 1826(S) in MIP-2 promoter activity. These results perhaps give more insights into understanding of the mechanisms involved in transient inflammatory arthritis induction by CpG-ODN treatment.
Kwon
Hyung-Joo
HJ
Institute of Life Science and Biotechnology, College of Science, Yonsei University, Seoul, South Korea.
Kim
Doo-Sik
DS
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051996:Transcription Factor RelA; D015533:Transcriptional Activation
D054426:Chemokine CXCL2; D018925:Chemokines; C423449:CpG ODN 1826; C404915:Cxcl2 protein, mouse; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D051996:Transcription Factor RelA; D004247:DNA