NF-kappaB-dependent regulation of matrix metalloproteinase-9 gene expression by lipopolysaccharide in a macrophage cell line RAW 264.7.
Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in the turnover of extracellular matrix (ECM) and in the migration of normal and tumor cells in response to normal physiologic and numerous pathologic conditions. Here, we show that the transcription of the MMP-9 gene is induced by lipopolysaccharide (LPS) stimulation in cells of a macrophage lineage (RAW 264.7 cells). We provide evidence that the NF-kappaB binding site of the MMP-9 gene contributes to its expression in the LPS-signaling pathway, since mutation of NF-kappaB binding site of MMP-9 promoter leads to a dramatic reduction in MMP-9 promoter activation. In addition, the degradation of IkappaBalpha, and the presences of myeloid differentiation protein (MyD88) and tumor necrosis factor receptor-associated kinase 6 (TRAF6) were found to be required for LPS-activated MMP-9 expression. Chromatin immunoprecipitation (ChIP) assays showed that functional interaction between NF-kappaB and the MMP-9 promoter element is necessary for LPS-activated MMP-9 induction in RAW 264.7 cells. In conclusion, our observations demonstrate that NF-kappaB contributes to LPS-induced MMP-9 gene expression in a mouse macrophage cell line.
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
Kim
Dongbum
D
Lee
Younghee
Y
Jeon
Ok-Hee
OH
Kwon
Hyung-Joo
HJ
Kim
Doo-Sik
DS
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D020780:Matrix Metalloproteinase 9