Melatonin attenuates expression of cyclooxygenase-2 (COX-2) in activated microglia induced by lipopolysaccharide (LPS)

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-kappa B, the upstream signal pathways of COX-2. Taken together, evidence indicates that MEL may attenuate upregulation of COX-2 by blocking the MAPK/NF-kappa B signaling pathway in LPS-stimulated microglia.