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

Che Chao Chang, Chih Hao Tien, E. Jian Lee, Wei Sheng Juan, Ying Hsin Chen, Yu Chang Hung, Tsung Ying Chen, Hung Yi Chen, Tian Shung Wu

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)188-197
Number of pages10
JournalJournal of Pineal Research
Volume53
Issue number2
DOIs
Publication statusPublished - 2012 Sep 1

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Matrix Metalloproteinase 9
Melatonin
Meningitis
Lipopolysaccharides
NF-kappa B
RAW 264.7 Cells
Matrix Metalloproteinase 2
Metalloproteases
Electrophoretic Mobility Shift Assay
Encephalitis
Gelatin
Anti-Inflammatory Agents
Immunohistochemistry
Body Weight
Inflammation
Therapeutics

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

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title = "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",
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.",
author = "Chang, {Che Chao} and Tien, {Chih Hao} and Lee, {E. Jian} and Juan, {Wei Sheng} and Chen, {Ying Hsin} and Hung, {Yu Chang} and Chen, {Tsung Ying} and Chen, {Hung Yi} and Wu, {Tian Shung}",
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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. / Chang, Che Chao; Tien, Chih Hao; Lee, E. Jian; Juan, Wei Sheng; Chen, Ying Hsin; Hung, Yu Chang; Chen, Tsung Ying; Chen, Hung Yi; Wu, Tian Shung.

In: Journal of Pineal Research, Vol. 53, No. 2, 01.09.2012, p. 188-197.

Research output: Contribution to journalArticle

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T1 - 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

AU - Chang, Che Chao

AU - Tien, Chih Hao

AU - Lee, E. Jian

AU - Juan, Wei Sheng

AU - Chen, Ying Hsin

AU - Hung, Yu Chang

AU - Chen, Tsung Ying

AU - Chen, Hung Yi

AU - Wu, Tian Shung

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