These two authors have made equal contributions to the study.
Melatonin inhibits matrix metalloproteinase-9 (MMP-9) activation in the lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells and a mouse model of meningitis
Article first published online: 8 MAR 2012
© 2012 John Wiley & Sons A/S
Journal of Pineal Research
Volume 53, Issue 2, pages 188–197, September 2012
How to Cite
Chang, C.-C., Tien, C.-H., Lee, E.-J., Juan, W.-S., Chen, Y.-H., Hung, Y.-C., Chen, T.-Y., Chen, H.-Y. and Wu, T.-S. (2012), Melatonin inhibits matrix metalloproteinase-9 (MMP-9) activation in the lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells and a mouse model of meningitis. Journal of Pineal Research, 53: 188–197. doi: 10.1111/j.1600-079X.2012.00986.x
- Issue published online: 13 AUG 2012
- Article first published online: 8 MAR 2012
- Accepted manuscript online: 15 FEB 2012 03:30PM EST
- Received January 5, 2012; Accepted February 10, 2012.
- matrix metalloproteinase-9;
- nuclear factor-kappa B
Abstract: We explored anti-inflammatory potential of melatonin against the lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. RAW 264.7 and BV2 cells were stimulated by LPS, followed by the treatment with melatonin or vehicle at various time intervals. In a mouse model of meningitis induced by LPS, melatonin (5 mg/kg) or vehicle was intravenously injected at 30 min postinsult. The activity of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was determined by gelatin zymography. Nuclear factor-kappa B (NFκB) translocation and binding activity were determined by immunocytochemistry and electrophoretic mobility shift assay (EMSA). Our results showed that either pretreatment or cotreatment with melatonin at 50–500 μm effectively inhibited the LPS-induced proMMP-9 activation in the RAW 264.7 and BV2 cells, respectively (P < 0.05). This melatonin-induced proMMP-9 inhibition remained effective when treatment was delayed up to 2 and 6 hr postinsult for RAW 264.7 and BV2 cells, respectively (P < 0.05 for both groups). Additionally, melatonin significantly attenuated the rises of circulatory and cerebral MMP-9 activity, respectively (P < 0.05) and reduced the loss of body weight (P < 0.05) in mice with meningitis. Moreover, melatonin (50 μm) effectively inhibited nuclear factor-kappa B (NFκB) translocation and binding activity in the LPS-treated RAW 264.7 and BV2 cells, respectively (P < 0.05). These results demonstrate direct inhibitory actions of melatonin against postinflammatory NFκB translocation and MMP-9 activation and highlight its ability to inhibit systemic and cerebral MMP-9 activation following brain inflammation.