title: Interaction of monocytes with vascular endothelial cells synergistically induces interferon gamma-inducible protein 10 expression through activation of specific cell surface molecules and cytokines.
abstract: To further understand the regulatory mechanisms involved in the process of angiogenesis, the present study was designed to determine the expression and regulation of interferon gamma-inducible protein 10 (IP-10) in peripheral blood monocytes and human umbilical vein endothelial cells (HUVECs). We found that the interaction of monocytes with HUVECs resulted in synergistic increases in IP-10 expression and secretion, which consequently inhibited endothelial tube formation in vitro. Induction of IP-10 was mediated via specific cell surface molecules, as indicated by the finding that IP-10 secretion was significantly inhibited by anti-CD40 ligand antibody, and to a lesser extent by anti-CD40 antibody. Furthermore, we examined the effects of soluble mediators, such as inflammatory and immune cytokines on IP-10 secretion. Addition of interleukin (IL)-1, as well as interferon gamma, induced a marked augmentation of IP-10 secretion by unstimulated monocytes, unstimulated HUVECs, and co-cultures of the two cell types. In contrast, IL-10, recognized as an anti-inflammatory cytokine, significantly inhibited IP-10 secretion by co-cultures. Our results suggest that the interaction of monocytes with endothelial cells results in synergistic increases in IP-10 expression and secretion, which contribute to the regulation of angiogenesis and initiation of inflammatory vascular diseases.
authors.affiliation: Division of Rheumatology and Clinical Immunology, First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. tkasama@med.showa-u.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kasama
authors.forename: Mizuho
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yajima
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Shiozawa
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hanaoka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miwa
authors.forename: Masao
authors.initials: M
authors.lastname: Negishi
authors.forename: Hirotugu
authors.initials: H
authors.lastname: Ide
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
mesh_terms: D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis*; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000276:immunology; D014471:Umbilical Veins; D015854:Up-Regulation
chemical_list: D019013:CD40 Antigens; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007375:Interleukin-1; D016753:Interleukin-10; D023201:CD40 Ligand; D007371:Interferon-gamma