title: The brominated compound aeroplysinin-1 inhibits proliferation and the expression of key pro- inflammatory molecules in human endothelial and monocyte cells.
abstract: Aeroplysinin-1 is a brominated antibiotic used by some sponges for defense against bacterial pathogen invasion. Aeroplysinin-1 has a wide spectrum of anti-tumoral action and behaves as a potent anti-angiogenic compound for bovine aortic endothelial cells. In this study, we demonstrate anti-angiogenic effects of aeroplysinin-1 on human endothelial cells. Furthermore, the response of angiogenesis related genes to aeroplysinin-1 treatment was studied in human endothelial cells by using gene arrays. The major changes were observed in thrombospondin 1 (TSP-1) and monocyte chemoattractant protein-1 (MCP-1), both of which were down-regulated. These inhibitory effects of aeroplysinin-1 were confirmed by using independent experimental approaches. To have a deeper insight on the anti-inflammatory effects of aeroplysinin-1 in endothelial cells, cytokine arrays were also used. This experimental approach confirmed effects on MCP-1 and TSP-1 and showed down-regulation of several other cytokines. Western blotting experiments confirmed down-regulation of ELTD1 (EGF, latrophilin and seven transmembrane domain-containing protein 1), interleukin 1α and matrix metalloproteinase 1 (MMP-1). These results along with our observation of a dramatic inhibitory effect of aeroplysinin-1 on cyclooxygenase-2 protein expression levels in endothelial cells and a human monocyte cell line suggest that aeroplysinin-1 could be a novel anti-inflammatory compound with potential pharmacological interest.
authors: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga, Spain.
authors: Beatriz
authors: B
authors: Martínez-Poveda
authors: Javier A
authors: JA
authors: García-Vilas
authors: Casimiro
authors: C
authors: Cárdenas
authors: Esther
authors: E
authors: Melgarejo
authors: Ana R
authors: AR
authors: Quesada
authors: Miguel A
authors: MA
authors: Medina
mesh_terms: D000097:Acetonitriles / Q000032:analysis / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D053138:Cyclohexenes / Q000032:analysis / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009000:Monocytes / Q000378:metabolism*; D011161:Porifera / Q000737:chemistry*; D013778:Tetrazolium Salts; D013844:Thiazoles; D019700:Thrombospondin 1 / Q000378:metabolism
chemical_list: D000097:Acetonitriles; D020533:Angiogenesis Inhibitors; D018932:Chemokine CCL2; D053138:Cyclohexenes; D052246:Cyclooxygenase 2 Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D019700:Thrombospondin 1; C042151:aeroplysinin I; C022616:thiazolyl blue
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