| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5506184 | Biochemical and Biophysical Research Communications | 2017 | 7 Pages |
•Melatonin suppresses inflammatory responses by uncertain mechanisms in macrophage.•Microarray analysis and TFs binding site analysis were performed for this purpose.•Results showed melatonin inhibited various pathways thru HIF1α as well as IRF, NF-κB.•Melatonin destabilized actin cytoskeleton and impaired phagocytosis.•Melatonin regulates inflammations by inhibiting TFs by disrupting actin dynamics.
Melatonin produced by the pineal gland suppresses inflammatory responses in innate immune cells. However, the mechanism of how melatonin affects inflammatory gene regulation remains unclear. Here we performed comprehensive microarray analysis combined with transcription factor binding site (TFBS) analysis using LPS-induced mouse macrophages to investigate the effect of melatonin treatment. The results showed that melatonin preferentially downregulated interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) related signaling. The results also showed that melatonin strongly suppressed virus infection related gene expression. Furthermore, TFBS analysis implicated that melatonin downregulated the binding activity of hypoxia inducible factors (HIFs), following destabilizing actin cytoskeleton which are indispensable for induction of the TRIF-dependent signaling pathway. Indeed, it was demonstrated that melatonin treatment caused impaired phagocytosis in macrophages. Thus, melatonin regulates inflammatory responses by inhibiting specific subsets of transcription factors (TFs) by disrupting actin dynamics in the macrophage.
