Abstract
Background
Idiopathic 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 TGFβ1-dependent responses in IPF and non-fibrotic control (NFC) HLMFs.
Methods
HLMFs were isolated from IPF and NFC patients and grown in vitro. The effects of LXA4 were examined on myofibroblast wound healing, collagen secretion, and αSMA expression were examined in association with the Smad 2/3 pathway.
Results
LXA4 significantly inhibited FBS-dependent HLMF wound healing (P=0.0365) and TGFβ1-stimulted collagen secretion 10 pM (P=0.0201) and 10 nM (P=0.0190). Furthermore, LXA4 reduced constitutive αSMA expression indicating regression from a myofibroblast to fibroblast phenotype (P=0.0212). LXA4 also significantly attenuated TGFβ-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.
- © 2014 ERS