Background: Pulmonary fibrosis (PF) is a form of progressive lung disease characterized by epithelial-endothelial mesenchymal transition (EMT) and extracellular matrix deposition.

Aim: We aimed to test Imatinib (an anti-remodelling Tyrosine-Kinase inhibitors) activity in an innovative ?in vitro? model of EMT, which is obtained in human precision cut lung slices (PCLS).

Methods: PCLS (obtained by normal lung tissue) within 4 hrs from retrieval, were cultured for up to 72 hrs in presence of: a) Platelet Lysate (LP) (3%) + TGF-? (10ng/mL); b) Neutrophil Extracellular Traps (NETs) (from 100 nM PMA stimulation of 5x106 Neutrophils). 15 µM Imatinib was added to certain PCLS. Markers of EMT were detected at 24-48-72 hrs of culture: expression of ?-SMA (ACTA2), Collagen1a1 (COL1a1) and Collagen3a1 (COL3a1) by RT-PCR and protein levels at 48-72 hrs by WB analysis.

Results: Expression profiles with both stimulations showed an increase of all markers by 24 to 72 hrs. Surprisingly, Imatinib alone caused an increase in the expression levels of COL1a, COL3a1 and ?-SMA compared to untreated slices. This drug, when added to LP-TGF? or to NETs significantly down regulated or abolished the expression ?-SMA, COL1a1, COL3a1. All data were confirmed by WB analysis at 72 hrs.

Conclusion: PCLS allow the generation of a ?whole lung? EMT model useful to assess the activity of anti-remodeling therapeutic strategies.