NF-κB-dependent Regulation of Matrix Metalloproteinase-9 Gene Expression by Lipopolysaccharide in a Macrophage Cell Line RAW 264.7

Abstract

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.