title: Angiopoietin-like protein 2 induces proinflammatory responses in peritoneal cells.
abstract: Monocytes and macrophages are important effectors and regulators of inflammation, and both their differentiation and activation are regulated strictly in response to environmental cues. Angiopoietin-like protein 2 (Angptl2) is a multifaceted protein, displaying many physiological and pathological functions in inflammation, angiogenesis, hematopoiesis, and tumor development. Although recent studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation caused by Angptl2 remain unclear. The purpose of the present study was to elucidate the role of Angptl2 in inflammation by understanding the effects of Angptl2 on monocytes/macrophages. We showed that Angptl2 directly activates resident murine peritoneal monocytes and macrophages and induces a drastic upregulation of the transcription of several inflammatory genes including nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, and several proinflammatory cytokine genes such as interleukin (IL)-1β, IL-6, TNFα, and CSF2, along with activation of ERK, JNK, p38, and nuclear factor kappa B signaling pathways. Concordantly, proinflammatory cytokines IL-1β, IL-6, TNFα, and GM-CSF, were rapidly elevated from murine peritoneal monocytes and macrophages. These results demonstrate a novel role for Angptl2 in inflammation via the direct activation of peritoneal monocytes and macrophages.
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. Electronic address: umikawa@med.u-ryukyu.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Umikawa
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Umikawa
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Asato
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Takei
authors.affiliation: Department of Tropical Infectious Diseases, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kariya
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: alec.zhang@utsouthwestern.edu.
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
mesh_terms: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000276:immunology*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology
chemical_list: C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cytokine production; Inflammation; Macrophage; Monocyte; Peritoneal cells