IL-1β induces MMP-9 via reactive oxygen species and NF-κB in murine macrophage RAW 264.7 cells

• Published in: Biochemical and biophysical research communications Vol. 298; no. 2; pp. 251 - 256
• Main Authors: Yoo, Hyeon G, Shin, Boo.A, Park, Jung S, Lee, Kee H, Chay, Kee O, Yang, Sung Y, Ahn, Bong W, Jung, Young D
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 25-10-2002
• Subjects: IL-1β; Macrophage; MMP-9; NF-κB; ROS; NF-κB; IL-1β; MMP-9; ROS; Macrophage
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)02431-2

IL-1β increased the production of proenzyme of MMP-9 (pro-MMP-9) in a time- and dose-dependent manner in murine macrophage RAW 264.7 cells. However, the production of MMP-2 was not significantly changed by IL-1β treatment. The intracellular H
2O
2 content, as determined with H
2O
2-sensitive probe 2
′,7
′-dichlorodihydrofluorescein, also increased after IL-1β treatment (5
ng/ml). In addition, exogenous H
2O
2 (50
μM) was found to increase the production of pro-MMP-9. Transient transfection study using a MMP-9 promoter–reporter construct showed that IL-1β enhanced the MMP-9 promoter activity. Electrophoretic mobility shift assay and site-directed mutagenesis study on the consensus binding site for NF-κB revealed that the activation of NF-κB is required for the IL-1β-induced activation of MMP-9 promoter. N-acetylcysteine, an antioxidant, could abrogate the production of pro-MMP-9, H
2O
2 generation, and activation of NF-κB and MMP-9 promoter. These results suggest that IL-1β upregulates the MMP-9 expression via production of reactive oxygen species and activation of NF-κB in RAW 264.7 cells.