RRC ID 42934
著者 Hayashi M, Shimba S, Tezuka M.
タイトル Characterization of the molecular clock in mouse peritoneal macrophages.
ジャーナル Biol Pharm Bull
Abstract Macrophages play essential roles in the innate immune system. In this study, we show that macrophage functions such as phagocytosis and cytokine/chemokine expressions display a circadian rhythm that is regulated by a molecular clock. Phagocytosis, a crucial early reaction by which macrophages protect their host against foreign particles, exhibited a circadian variation that peaks during the light period and bottoms during the dark period. These diurnal changes of phagocytosis activity in macrophages were induced without exogenous stimulants such as bacterial infection. The expression of the clock genes including brain and muscle Arnt-like protein-1 (BMAL1) exhibited robust circadian rhythms in macrophages. The expression patterns of the clock genes in macrophages were similar to those in the suprachiasmatic nucleus and other peripheral tissues. Among inflammation factors examined, the level of monocyte chemoattractant protein-1 (MCP-1/JE) mRNA exhibited most robust circadian oscillation. Expression of other cytokines such as IL-1beta, IL-6 and TNFalpha showed mild diurnal changes. Knockdown of the BMAL1 expression resulted in a decrease of the MCP-1/JE mRNA level in macrophages. BMAL1 increased significantly but weakly MCP-1/JE promoter activity. MCP-1/JE promoter activity is known to be regulated by nuclear factor-kappa B (NF-kappaB). NF-kappaB activity in BMAL1 knockdown macrophages was lower than that in control cells. Consequently, the circadian expression of MCP-1/JE in macrophages is regulated by BMAL1 through the activation of NF-kappaB. The results obtained in this study indicate that the innate immunoreactions involving macrophages are at least partly regulated by the autonomous clock machinery.
巻・号 30(4)
ページ 621-6
公開日 2007-4-1
DOI 10.1248/bpb.30.621
PII JST.JSTAGE/bpb/30.621
PMID 17409491
MeSH ARNTL Transcription Factors Animals Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism Biological Clocks / physiology* Cell Line Chemokine CCL2 / genetics Chemokine CCL2 / metabolism Circadian Rhythm* Fluorescein-5-isothiocyanate Fluorescent Dyes Gene Expression Genes, Reporter Interleukin-1beta / genetics Interleukin-1beta / metabolism Interleukin-6 / genetics Interleukin-6 / metabolism Macrophages, Peritoneal / physiology* Male Mice Mice, Inbred C57BL Opsonin Proteins / metabolism Phagocytosis RNA, Messenger / metabolism RNA, Small Interfering / metabolism Receptors, Chemokine / genetics Receptors, Chemokine / metabolism Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism Zymosan / pharmacology
IF 1.863
引用数 112
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)