Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases.
During angiogenesis and inflammatory processes, endothelial cells acquire different activation phenotypes, whose identification may help in understanding the complex network of angiogenic and inflammatory interactions in vivo. To this goal we investigated the expression of the human guanylate-binding protein (GBP)-1 that is highly induced by inflammatory cytokines (ICs) and, therefore, may characterize IC-activated cells. Using a new rat monoclonal antibody raised against GBP-1, we show that GBP-1 is a cytoplasmic protein and that its expression in endothelial cells is selectively induced by interferon-gamma, interleukin-1alpha, interleukin-1beta, or tumor necrosis factor-alpha, but not by other cytokines, chemokines, or growth factors. Moreover, we found that GBP-1 expression is highly associated with vascular endothelial cells as confirmed by the simultaneous detection of GBP-1 and the endothelial cell-associated marker CD31 in a broad range of human tissues. Notably, GBP-1 expression was undetectable in the skin, but it was highly induced in vessels of skin diseases with a high-inflammatory component including psoriasis, adverse drug reactions, and Kaposi's sarcoma. These results indicate that GBP-1 is a novel cellular activation marker that characterizes the IC-activated phenotype of endothelial cells.
Lubeseder-Martellato
Clara
C
Department of Virus-Induced Vasculopathy, Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Neuherberg, Germany.
Guenzi
Eric
E
Jörg
Anita
A
Töpolt
Kristin
K
Naschberger
Elisabeth
E
Kremmer
Elisabeth
E
Zietz
Christian
C
Tschachler
Erwin
E
Hutzler
Peter
P
Schwemmle
Martin
M
Matzen
Kathrin
K
Grimm
Thomas
T
Ensoli
Barbara
B
Stürzl
Michael
M
D015415:Biomarkers / Q000032:analysis; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D011565:Psoriasis / Q000097:blood / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000378:metabolism; D012871:Skin Diseases / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D014018:Tissue Distribution
D015415:Biomarkers; D016207:Cytokines; D004268:DNA-Binding Proteins; C490287:GBP1 protein, human; D007371:Interferon-gamma; D019204:GTP-Binding Proteins