title: Microarray and gene co-expression analysis reveals that melatonin attenuates immune responses and modulates actin rearrangement in macrophages.
abstract: 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.
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan; Department of Special Needs Dentistry, Division of Dentistry for Persons with Disabilities, School of Dentistry, Showa University, Kitasenzoku 2-1-1, Ohta-ku, Tokyo, 145-8515, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kadena
authors.affiliation: Quantitative Immunology Research Unit, Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.affiliation: Immuno-Genomics Research Unit, Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vandenbon
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Matsushima
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Fukamachi
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Maruta
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Arimoto
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Morisaki
authors.affiliation: Department of Special Needs Dentistry, Division of Dentistry for Persons with Disabilities, School of Dentistry, Showa University, Kitasenzoku 2-1-1, Ohta-ku, Tokyo, 145-8515, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Funatsu
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. Electronic address: hkuwata@dent.showa-u.ac.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kuwata
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D058105:Polymerization / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000199:Actins; D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D008550:Melatonin
keywords: Inflammation; Macrophage; Melatonin; Microarray analysis; Transcription factor