Regulation of matrix metalloproteinase-9 gene expression and cell migration by NF-kappa B in response to CpG-oligodeoxynucleotides in RAW 264.7 cells.
Matrix metalloproteinase-9 (MMP-9) is a secreted type IV collagenase that plays an important role in the remodeling of the extracellular matrix (ECM) and the migration of normal and tumor cells. We have shown that CpG-ODN-induced migration of RAW 264.7 cell is regulated by MMP-9 activity by using tissue inhibitors of MMP-1 (TIMP-1). The MMP-9 gene expression was transcriptionally induced by CpG-ODN in a time-dependent manner. An MMP-9 promoter-reporter was activated by the stimulation of CpG-ODN and ectopical expression of NF-kappaB transcription factor. Inhibition of NF-kappaB nuclear localization by co-expression of a mutant IkappaBalpha protein blocked the CpG-ODN-induced MMP-9 promoter activation. BMS-345541, an IKK-2 inhibitor also inhibited the expression of MMP-9 gene induced by CpG-ODN. Direct binding of NF-kappaB protein to the promoter region of the MMP-9 was confirmed by chromatin immunoprecipitation using NF-kappaB antibody. These results lead us to a conclusion that NF-kappaB activation is required for MMP-9 gene expression. In summary, our data suggest that NF-kappaB-dependent expression of MMP-9 in response to CpG-ODN plays an important role in the recruitment of immune cells.
Rhee
Jae Won
JW
Department of Biochemistry and Institute of Life Science and Biotechnology, College of Science, Yonsei University, Seoul 120-749, Republic of Korea.
Lee
Keun-Wook
KW
Sohn
Wern-Joo
WJ
Lee
Younghee
Y
Jeon
Ok-Hee
OH
Kwon
Hyung-Joo
HJ
Kim
Doo-Sik
DS
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology*
D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse