Melatonin modulates microsomal PGE synthase 1 and NF-E2-related factor-2-regulated antioxidant enzyme expression in LPS-induced murine peritoneal macrophages.

BACKGROUND AND
PURPOSE: Increasing evidence demonstrates that melatonin regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses. Nevertheless, the molecular mechanisms of its anti-inflammatory action remain unclear. Here we have characterized the cellular mechanisms underlying the redox modulation of LPS-stimulated inflammatory responses in murine peritoneal macrophages by melatonin to provide insight into its anti-inflammatory effects. EXPERIMENTAL APPROACH: Murine peritoneal macrophages were isolated and treated with melatonin in the presence or absence of LPS (5 μg·mL(-1) ) for 18 h. Cell viability was determined using sulforhodamine B assay and NO production was measured using the Griess reaction. Pro-inflammatory enzymes and transcription factors were detected by Western blotting. KEY
RESULTS: Without affecting cell viability, melatonin (12.5, 25, 50 and 100 μM) reduced the level of nitrites, inducible NOS (iNOS), COX-2 and microsomal PGE synthase-1 (mPGES1) protein, and p38 MAPK phosphorylation, and prevented NF-κB translocation. Furthermore, melatonin treatment significantly increased NF-E2-related factor 2 (Nrf2) and haem oxygenase 1 (HO1) protein levels in murine macrophages exposed to LPS. CONCLUSIONS AND IMPLICATIONS: Melatonin reduced pro-inflammatory mediators and enhanced the expression of HO1 via NF-κB, p38 MAPK and Nrf2 cascade signalling pathways in murine macrophages. Thus, melatonin might be a promising target for diseases associated with overactivation of macrophages.