Open AccessPro-Resolving Effects of Resolvin D2 in LTD4 and TNF-α Pre-Treated Human Bronchi
Author(s) -
Rayan KhaddajMallat,
Chantal Sirois,
Marco Sirois,
Edmond Rizcallah,
Sofia Marouan,
Caroline Morin,
Éric Rousseau
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0167058
Subject(s) - inflammation , leukotriene d4 , receptor , pharmacology , tumor necrosis factor alpha , leukotriene , respiratory system , medicine , chemistry , asthma
Inflammation is a major burden in respiratory diseases, resulting in airway hyperresponsiveness. Our hypothesis is that resolution of inflammation may represent a long-term solution in preventing human bronchial dysfunctions. The aim of the present study was to assess the anti-inflammatory effects of RvD 2 , a member of the D-series resolving family, with concomitant effects on ASM mechanical reactivity. The role and mode of action of RvD 2 were assessed in an in vitro model of human bronchi under pro-inflammatory conditions, induced either by 1 μM LTD 4 or 10 ng/ml TNF-α pre-treatment for 48h. TNF-α and LTD 4 both induced hyperreactivity in response to pharmacological stimuli. Enhanced 5-Lipoxygenase (5-LOX) and cysteinyl leukotriene receptor 1 ( CysLTR1 ) detection was documented in LTD 4 or TNF-α pre-treated human bronchi when compared to control (untreated) human bronchi. In contrast, RvD 2 treatments reversed 5-LOX/β-actin and CysLTR1/β-actin ratios and decreased the phosphorylation levels of AP-1 subunits (c-Fos, c-Jun) and p38-MAP kinase, while increasing the detection of the ALX/FPR2 receptor. Moreover, various pharmacological agents revealed the blunting effects of RvD 2 on LTD 4 or TNF-α induced hyper-responsiveness. Combined treatment with 300 nM RvD 2 and 1 μM WRW4 (an ALX/FPR2 receptor inhibitor) blunted the pro-resolving and broncho-modulatory effects of RvD 2 . The present data provide new evidence regarding the role of RvD 2 in a human model of airway inflammation and hyperrresponsiveness.