title: Regulation of matrix metalloproteinase-9 gene expression and cell migration by NF-kappa B in response to CpG-oligodeoxynucleotides in RAW 264.7 cells.
abstract: 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.
authors.affiliation: Department of Biochemistry and Institute of Life Science and Biotechnology, College of Science, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Rhee
authors.forename: Keun-Wook
authors.initials: KW
authors.lastname: Lee
authors.forename: Wern-Joo
authors.initials: WJ
authors.lastname: Sohn
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Jeon
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kim
mesh_terms: 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*
chemical_list: D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse