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Published on: October 17, 2018
Melatonin attenuates expression of cyclooxygenase-2 (COX-2) in activated microglia induced by lipopolysaccharide
Chunyan Yao1, Xiaoling Liu1, Zhengyu Zhou1
1a Department of Epidemiology , College of Preventive Medicine, Army Medical University (Third Military Medical University) , Chongqing , China.
Abstract:
Lipopolysaccharide (LPS) is a known neurotoxin and utilized most extensively as a microglial activator for induction of inflammatory neurodegeneration. Melatonin (MEL) is the main secretory product of pineal gland reported to be responsible for a variety of physiological functions. However, the molecular mechanisms underlying the influence of MEL on microglia activation remain unclear. The aim of this study was to investigate the effect of MEL on cyclooxygenase-2 (COX-2) levels in LPS-induced microglia. The results of RT-PCR and Western blot analysis showed that MEL significantly inhibited LPS-mediated upregulation of COX-2 in microglia. Data from ELISA demonstrated that prostaglandin E2 (PGE2), the downstream effector of COX-2, concentrations were also reduced. In addition, MEL was found to decrease activation of ERK1/2, JNK, p38 MAPK, and NF-κB, the upstream signal pathways of COX-2. Taken together, evidence indicates that MEL may attenuate upregulation of COX-2 by blocking the MAPK/NF-κB signaling pathway in LPS-stimulated microglia.
Insights
Melatonin (MEL) reduces neuroinflammation by inhibiting lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) in microglia. This occurs by blocking key signaling pathways like MAPK and NF-κB, offering potential therapeutic benefits.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Lipopolysaccharide (LPS) is a potent neurotoxin that activates microglia, leading to inflammatory neurodegeneration.
- Melatonin (MEL), a pineal gland hormone, has diverse physiological roles, but its effects on microglia activation are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms by which MEL influences microglia activation, specifically its effect on cyclooxygenase-2 (COX-2) expression in LPS-induced microglia.
Main Methods:
- Quantitative RT-PCR and Western blot analysis were used to assess COX-2 expression.
- Enzyme-linked immunosorbent assay (ELISA) measured prostaglandin E2 (PGE2) levels.
- Analysis of upstream signaling pathways including ERK1/2, JNK, p38 MAPK, and NF-κB activation.
Main Results:
- MEL significantly inhibited LPS-induced upregulation of COX-2 in microglia.
- MEL treatment led to reduced concentrations of PGE2, a downstream product of COX-2.
- MEL decreased the activation of ERK1/2, JNK, p38 MAPK, and NF-κB signaling pathways.
Conclusions:
- Melatonin attenuates the upregulation of COX-2 in LPS-stimulated microglia.
- The anti-inflammatory effects of MEL on microglia are mediated through the inhibition of the MAPK/NF-κB signaling pathway.
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