Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells

Giulia Salazar, Chiara Bellocchi, Katia Todoerti, Federica Saporiti, Luca Piacentini, Raffaella Scorza, Gualtiero Colombo

Research output: Contribution to journalArticle

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 100 U/ml in the presence or absence of Aminaphtone 6 μg/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray. Supernatants of ECV-304 cultures were analysed at 3, 6, 12, and 24 h 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.

Original languageEnglish
Pages (from-to)59-69
Number of pages11
JournalEuropean Journal of Pharmacology
Volume782
DOIs
Publication statusPublished - Jul 5 2016

Fingerprint

Gene Expression Profiling
Endothelial Cells
Cytokines
Chemokines
Venous Insufficiency
Cytokine Receptors
Body Fluids
Endothelin-1
Interleukin-1
Transcriptome
Cell Communication
Cell Division
Genes
Atherosclerosis
Homeostasis
Fibrosis
Transcription Factors
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Cell Proliferation

Keywords

  • Cytokines
  • Endothelial cells
  • Endothelin-1
  • Gene expression profiling
  • Inflammation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells. / Salazar, Giulia; Bellocchi, Chiara; Todoerti, Katia; Saporiti, Federica; Piacentini, Luca; Scorza, Raffaella; Colombo, Gualtiero.

In: European Journal of Pharmacology, Vol. 782, 05.07.2016, p. 59-69.

Research output: Contribution to journalArticle

Salazar, Giulia ; Bellocchi, Chiara ; Todoerti, Katia ; Saporiti, Federica ; Piacentini, Luca ; Scorza, Raffaella ; Colombo, Gualtiero. / Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells. In: European Journal of Pharmacology. 2016 ; Vol. 782. pp. 59-69.
@article{21baf9b5a22b432daff0ac7f6a4bb4a1,
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 100 U/ml in the presence or absence of Aminaphtone 6 μg/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray. Supernatants of ECV-304 cultures were analysed at 3, 6, 12, and 24 h 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.",
keywords = "Cytokines, Endothelial cells, Endothelin-1, Gene expression profiling, Inflammation",
author = "Giulia Salazar and Chiara Bellocchi and Katia Todoerti and Federica Saporiti and Luca Piacentini and Raffaella Scorza and Gualtiero Colombo",
year = "2016",
month = "7",
day = "5",
doi = "10.1016/j.ejphar.2016.04.018",
language = "English",
volume = "782",
pages = "59--69",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

TY - JOUR

T1 - Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells

AU - Salazar, Giulia

AU - Bellocchi, Chiara

AU - Todoerti, Katia

AU - Saporiti, Federica

AU - Piacentini, Luca

AU - Scorza, Raffaella

AU - Colombo, Gualtiero

PY - 2016/7/5

Y1 - 2016/7/5

N2 - 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 100 U/ml in the presence or absence of Aminaphtone 6 μg/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray. Supernatants of ECV-304 cultures were analysed at 3, 6, 12, and 24 h 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.

AB - 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 100 U/ml in the presence or absence of Aminaphtone 6 μg/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray. Supernatants of ECV-304 cultures were analysed at 3, 6, 12, and 24 h 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.

KW - Cytokines

KW - Endothelial cells

KW - Endothelin-1

KW - Gene expression profiling

KW - Inflammation

UR - http://www.scopus.com/inward/record.url?scp=84964687221&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964687221&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2016.04.018

DO - 10.1016/j.ejphar.2016.04.018

M3 - Article

VL - 782

SP - 59

EP - 69

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -