BML-111 suppresses TGF-β1-induced lung fibroblast activation in vitro and decreases experimental pulmonary fibrosis in vivo.

Pulmonary fibrosis is an aggressive end‑stage disease. Transforming growth factor‑β1 (TGF‑β1) mediates lung fibroblast activation and is essential for the progress of pulmonary fibrosis. BML‑111, a lipoxinA4 (LXA4) receptor (ALX) agonist, has been reported to possess anti‑fibrotic properties. The present study aimed to elucidate whether BML‑111 inhibits TGF‑β1‑induced mouse embryo lung fibroblast (NIH3T3 cell line) activation in vitro and bleomycin (BLM)‑induced pulmonary fibrosis in vivo. In vitro experiments demonstrated that BML‑111 treatment inhibits TGF‑β1‑induced NIH3T3 cell viability and the expression of smooth muscle α actin (α‑SMA), fibronectin and total collagen. Furthermore, this suppressive effect was associated with mothers against decapentaplegic homolog (Smad)2/3, extracellular signal‑regulated kinase (ERK) and Akt phosphorylation interference. In vivo experiments revealed that BML‑111 treatment markedly improved survival rate and ameliorated the destruction of lung tissue structure. It also reduced interleukin‑1β (IL‑1β), tumor necrosis factor‑α (TNF‑α) and TGF‑β1 expression in the BLM intratracheal mouse model. In addition, the expression ofα‑SMA and extracellular matrix (ECM) deposition (total collagen, hydroxyproline and fibronectin) were also suppressed following BML‑111 treatment. However, BOC‑2, an antagonist of ALX, partially weakened the effects of BML‑111. In conclusion, these results indicated that BML‑111 inhibits TGF‑β1‑induced fibroblasts activation and alleviates BLM‑induced pulmonary fibrosis. Therefore, BML‑111 may be used as a potential therapeutic agent for pulmonary fibrosis treatment.