Lipoxin (LXA ₄ ) as a novel therapy for idiopathic pulmonary fibrosis

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 (LXA 4 ) is an anti-inflammatory lipid, important in the resolution of inflammation and has potential anti-fibrotic activity. However, the effects of LXA 4 on primary human lung myofibroblasts (HLMF) have not previously been investigated. Therefore, the aim of this study was to examine the effects of LXA 4 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 LXA 4 were examined on myofibroblast wound healing, collagen secretion, and αSMA expression were examined in association with the Smad 2/3 pathway. Results LXA 4 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, LXA 4 reduced constitutive αSMA expression indicating regression from a myofibroblast to fibroblast phenotype (P=0.0212). LXA 4 also significantly attenuated TGFβ-induced Smad 2/3 nuclear translocation. Conclusions We show for the first time that LXA 4 significantly attenuates pro-fibrotic myofibroblast function. LXA 4 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.