Interaction of monocytes with vascular endothelial cells synergistically induces interferon gamma-inducible protein 10 expression through activation of specific cell surface molecules and cytokines.
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.
Kasama
Tsuyoshi
T
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
Muramatsu
Mizuho
M
Kobayashi
Kazuo
K
Yajima
Nobuyuki
N
Shiozawa
Fumitaka
F
Hanaoka
Ryosuke
R
Miwa
Yusuke
Y
Negishi
Masao
M
Ide
Hirotugu
H
Adachi
Mitsuru
M
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
D019013:CD40 Antigens; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007375:Interleukin-1; D016753:Interleukin-10; D023201:CD40 Ligand; D007371:Interferon-gamma