Source: International Congress 2014 – New mechanisms in the pathogenesis of asthma and other lung diseases
Disease area: Interstitial lung diseases

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is a common, progressive and invariably lethal interstitial lung disease with no effective therapyThe key cell driving the development of fibrosis is the myofibroblast. Lipoxin (LXA₄) is an anti-inflammatory lipid, important in the resolution of inflammation and has potential anti-fibrotic activity. However, the effects of LXA₄ on primary human lung myofibroblasts (HLMF) have not previously been investigated. Therefore, the aim of this study was to examine the effects of LXA₄ on TGFb1-dependent responses in IPF and non-fibrotic control (NFC) HLMFs.MethodsHLMFs were isolated from IPF and NFC patients and grown in vitro. The effects of LXA₄ were examined on myofibroblast wound healing, collagen secretion, and aSMA expression were examined in association with the Smad 2/3 pathway.ResultsLXA₄ significantly inhibited FBS-dependent HLMF wound healing (P=0.0365) and TGFb1-stimulted collagen secretion 10 pM (P=0.0201) and 10 nM (P=0.0190). Furthermore, LXA₄ reduced constitutive aSMA expression indicating regression from a myofibroblast to fibroblast phenotype (P=0.0212). LXA₄ also significantly attenuated TGFb-induced Smad 2/3 nuclear translocation.Conclusions We show for the first time that LXA₄ significantly attenuates pro-fibrotic myofibroblast function. LXA₄ may therefore offer a novel approach to the treatment of IPF, with the potential for delivery as an aerosol.This work was funded by the MRC.

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Citations should be made in the following way:
K. M. Roach, L. Woodman, C. Feghali-Bostwick, P. Bradding (Leicester, United Kingdom; Pittsburgh, United States Of America). Lipoxin (LXA₄) as a novel therapy for idiopathic pulmonary fibrosis. Eur Respir J 2014; 44: Suppl. 58, 3877

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