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.
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.
Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea.
Kyoung-Jin
KJ
Min
Ji Hoon
JH
Jang
Taeg Kyu
TK
Kwon
D000818:Animals; D015153:Blotting, Western; D019742:Chemokines, CC / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000378:metabolism*
D019742:Chemokines, CC; D017931:DNA Primers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D050791:STAT Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D008550:Melatonin