Downregulation of NOX4 Expression by Roflumilast N-Oxide Reduces Markers of Fibrosis in Lung Fibroblasts
Joint Authors
Vecchio, Daniela
Tenor, Hermann
Gardi, Concetta
Arezzini, Beatrice
Martorana, Piero A.
Acquaviva, Alessandra
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-08-21
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
The phosphodiesterase 4 inhibitor roflumilast prevents bleomycin- (BLM-) induced lung fibrosis in animal models.
However, its mechanism of action remains unknown.
We investigated whether roflumilast N-oxide (RNO), the active metabolite of roflumilast, can modulate in vitro the oxidative effects of BLM on human lung fibroblasts (HLF).
In addition, since BLM increases the production of F2-isoprostanes that have per se fibrogenic activity, the effect of RNO on oxidative stress and fibrogenesis induced by the F2-isoprostane 8-epi-PGF2α was investigated.
HLF were preincubated either with the vehicle or with RNO and exposed to either BLM or 8-epi-PGF2α.
Proliferation and collagen synthesis were assessed as [3H]-thymidine and [3H]-proline incorporation.
Reactive oxygen species (ROS) and F2-isoprostanes were measured.
NADPH oxidase 4 (NOX4) protein and mRNA were also evaluated.
BLM increased both cell proliferation and collagen synthesis and enhanced ROS and F2-isoprostane production.
These effects were significantly prevented by RNO.
Also, RNO significantly reduced the increase in both NOX4 mRNA and protein, induced by BLM.
Finally, 8-epi-PGF2α per se stimulated HLF proliferation, collagen synthesis, and NOX4 expression and ROS generation, and RNO prevented these effects.
Thus, the antifibrotic effect of RNO observed in vivo may be related to its ability to mitigate ROS generation via downregulation of NOX4.
American Psychological Association (APA)
Vecchio, Daniela& Acquaviva, Alessandra& Arezzini, Beatrice& Tenor, Hermann& Martorana, Piero A.& Gardi, Concetta. 2013. Downregulation of NOX4 Expression by Roflumilast N-Oxide Reduces Markers of Fibrosis in Lung Fibroblasts. Mediators of Inflammation،Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-495371
Modern Language Association (MLA)
Vecchio, Daniela…[et al.]. Downregulation of NOX4 Expression by Roflumilast N-Oxide Reduces Markers of Fibrosis in Lung Fibroblasts. Mediators of Inflammation No. 2013 (2013), pp.1-8.
https://search.emarefa.net/detail/BIM-495371
American Medical Association (AMA)
Vecchio, Daniela& Acquaviva, Alessandra& Arezzini, Beatrice& Tenor, Hermann& Martorana, Piero A.& Gardi, Concetta. Downregulation of NOX4 Expression by Roflumilast N-Oxide Reduces Markers of Fibrosis in Lung Fibroblasts. Mediators of Inflammation. 2013. Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-495371
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-495371