Inhibitory effects of melatonin on the lipopolysaccharide-induced CC chemokine expression in BV2 murine microglial cells are mediated by suppression of Akt-induced NF-κB and STAT/GAS activity

• Published in: Journal of pineal research Vol. 52; no. 3; pp. 296 - 304
• Main Authors: Min, Kyoung-Jin, Jang, Ji Hoon, Kwon, Taeg Kyu
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2012
• Subjects: Akt; Animals; Blotting, Western; CC chemokine; Chemokines, CC - metabolism; DNA Primers; Enzyme-Linked Immunosorbent Assay; Lipopolysaccharides - pharmacology; melatonin; Melatonin - pharmacology; Mice; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; NF-kappa B - metabolism; NF-κB; Polymerase Chain Reaction; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Reverse Transcriptase Polymerase Chain Reaction; STAT; STAT Transcription Factors - metabolism
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/j.1600-079X.2011.00943.x

:  Melatonin influences sleep and circadian rhythm, and it has anti‐inflammatory functions. However, the mechanism of its anti‐inflammatory roles is not well understood. In our studies, we show that melatonin blocked lipopolysaccharide (LPS)‐induced CCL2 (monocyte chemotactic protein‐1; MCP‐1), CCL5 (Regulated upon Activation, Normal T‐cell Expressed, and Secreted), and CCL9 (macrophage inflammatory protein‐1γ) chemokine mRNA expression in BV2 murine microglial cells. Melatonin markedly inhibited LPS‐induced Akt phosphorylation and NF‐κB activation. Furthermore, melatonin inhibited LPS‐induced STAT1/3 phosphorylation and interferon‐gamma activated sequence (GAS)‐driven transcriptional activity. Interestingly, these effects were not associated with reactive oxygen species scavenging effects of melatonin or melatonin receptor signal pathways. Taken together, our results suggested that melatonin has anti‐inflammatory functions through down‐regulation of chemokine expression by inhibition of NF‐κB and STAT/GAS activation in LPS‐stimulated BV2 murine microglial cell line.