title: Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases.
abstract: 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.
authors.affiliation: Department of Virus-Induced Vasculopathy, Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Neuherberg, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Lubeseder-Martellato
authors.forename: Eric
authors.initials: E
authors.lastname: Guenzi
authors.forename: Anita
authors.initials: A
authors.lastname: Jörg
authors.forename: Kristin
authors.initials: K
authors.lastname: Töpolt
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Naschberger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Christian
authors.initials: C
authors.lastname: Zietz
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.forename: Peter
authors.initials: P
authors.lastname: Hutzler
authors.forename: Martin
authors.initials: M
authors.lastname: Schwemmle
authors.forename: Kathrin
authors.initials: K
authors.lastname: Matzen
authors.forename: Thomas
authors.initials: T
authors.lastname: Grimm
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Michael
authors.initials: M
authors.lastname: Stürzl
mesh_terms: 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
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004268:DNA-Binding Proteins; C490287:GBP1 protein, human; D007371:Interferon-gamma; D019204:GTP-Binding Proteins