title: Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells.
abstract: Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression and production of different inflammatory proteins. ECV-304 endothelial cells were stimulated with IL-1β 100U/ml in the presence or absence of Aminaphtone 6μg/ml. Gene expression profiles were compared at 1, 3, and 6h after stimulation by microarray. Supernatants of ECV-304 cultures were analysed at 3, 6, 12, and 24h by multiplex ELISA for production of several cytokine and chemokines. Microarrays showed a significant down-regulation at all times of a wide range of inflammatory genes. Aminaphtone appeared also able to modulate the regulation of immune response process (down-regulating cytokine biosynthesis, transcripts involved in lymphocyte differentiation and cell proliferation, and cytokine-cytokine receptor interaction) and to regulate genes engaged in homeostasis, secretion, body fluid levels, response to hypoxia, cell division, and cell-to-cell communication and signalling. Results were confirmed and extended analysing the secretome, which showed significant reduction of the release of 14 cytokines and chemokines. These effects are predicted to be mediated by interaction with different transcription factors. Aminaphtone was able to modulate the expression of inflammatory molecules relevant to the pathogenesis of several conditions in which the endothelial dysfunction is the main player and early event, like scleroderma, lung fibrosis, or atherosclerosis.
authors.affiliation: Referral Centre for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy. Electronic address: g.salazar@hotmail.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Salazar
authors.affiliation: Referral Centre for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellocchi
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-CROB, Referral Cancer Centre of Basilicata, Rionero in Vulture, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.affiliation: Laboratory of Immunology and Functional Genomics, Centro Cardiologico Monzino IRCCS, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Saporiti
authors.affiliation: Laboratory of Immunology and Functional Genomics, Centro Cardiologico Monzino IRCCS, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Piacentini
authors.affiliation: Referral Centre for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
authors.affiliation: Laboratory of Immunology and Functional Genomics, Centro Cardiologico Monzino IRCCS, Milan, Italy.
authors.forename: Gualtiero I
authors.initials: GI
authors.lastname: Colombo
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000494:pharmacology; D062366:para-Aminobenzoates / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D062366:para-Aminobenzoates; C016217:aminaftone
keywords: Aminaphtone (PubChem CID: 84621); Cytokines; Endothelial cells; Endothelin-1; Gene expression profiling; Inflammation