PMID- 23383109 OWN - NLM STAT- MEDLINE DCOM- 20130722 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 1 DP - 2013 TI - The brominated compound aeroplysinin-1 inhibits proliferation and the expression of key pro- inflammatory molecules in human endothelial and monocyte cells. PG - e55203 LID - 10.1371/journal.pone.0055203 [doi] LID - e55203 AB - 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 1alpha 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. FAU - Martinez-Poveda, Beatriz AU - Martinez-Poveda B AD - Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, Malaga, Spain. FAU - Garcia-Vilas, Javier A AU - Garcia-Vilas JA FAU - Cardenas, Casimiro AU - Cardenas C FAU - Melgarejo, Esther AU - Melgarejo E FAU - Quesada, Ana R AU - Quesada AR FAU - Medina, Miguel A AU - Medina MA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130128 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Acetonitriles) RN - 0 (Angiogenesis Inhibitors) RN - 0 (Chemokine CCL2) RN - 0 (Cyclohexenes) RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 0 (Tetrazolium Salts) RN - 0 (Thiazoles) RN - 0 (Thrombospondin 1) RN - 28656-91-9 (aeroplysinin I) RN - EUY85H477I (thiazolyl blue) SB - IM MH - Acetonitriles/analysis/*pharmacology MH - Angiogenesis Inhibitors/*pharmacology MH - Animals MH - Cell Proliferation/*drug effects MH - Chemokine CCL2/metabolism MH - Cyclohexenes/analysis/*pharmacology MH - Cyclooxygenase 2 Inhibitors/pharmacology MH - Endothelial Cells/*metabolism MH - Gene Expression Regulation/*drug effects MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Inhibitory Concentration 50 MH - Monocytes/*metabolism MH - Porifera/*chemistry MH - Tetrazolium Salts MH - Thiazoles MH - Thrombospondin 1/metabolism PMC - PMC3557235 COIS- Competing Interests: MAM is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2013/02/06 06:00 MHDA- 2013/07/23 06:00 PMCR- 2013/01/28 CRDT- 2013/02/06 06:00 PHST- 2012/07/30 00:00 [received] PHST- 2012/12/19 00:00 [accepted] PHST- 2013/02/06 06:00 [entrez] PHST- 2013/02/06 06:00 [pubmed] PHST- 2013/07/23 06:00 [medline] PHST- 2013/01/28 00:00 [pmc-release] AID - PONE-D-12-22649 [pii] AID - 10.1371/journal.pone.0055203 [doi] PST - ppublish SO - PLoS One. 2013;8(1):e55203. doi: 10.1371/journal.pone.0055203. Epub 2013 Jan 28.