Journal
FREE RADICAL RESEARCH
Volume 48, Issue 2, Pages 119-128Publisher
INFORMA HEALTHCARE
DOI: 10.3109/10715762.2013.845295
Keywords
melatonin; nitric oxide; glial cells; inflammation
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Funding
- Generalitat de Catalunya (autonomous government of Catalonia) [2009/SGR00853]
- Spanish Ministerio de Ciencia e Innovacion [BFU2010-19119/BFI, SAF2011-23631, SAF2012-39852-C02-01]
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Melatonin has been shown to down-regulate inflammatory responses and provide neuroprotection. However, the mechanisms underlying the anti-inflammatory properties of melatonin are poorly understood. In the present work, we studied the modulatory effect of melatonin against pro-inflammatory cytokines in glial cell cultures. Treatment with pro-inflammatory cytokines mainly tumor necrosis factor-alpha, interleukin 1-beta, and interferon-gamma induces an increase in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. Pre-treatment with melatonin produced an inhibitory effect on iNOS expression and NO production. The biochemical studies revealed that cytokine treatment favors the activation of several pathways, such as mitogen-activated protein kinases (MAPKs), STAT1, and STAT3; however, the anti-inflammatory effect of melatonin was accompanied only by a decrease in p38 MAPK activity. Likewise, SB203580 a p38 kinase inhibitor inhibits NO production. These data indicate that the anti-inflammatory action of melatonin in glial cells after stimulation with pro-inflammatory cytokines may be in part, attributable to p38 inhibition which down-regulates iNOS expression and NO production.
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