Objectives: to establish a murine model of bleomycin-induced pulmonary fibrosis, analysing the possible protective role of the Endocannabinoid System (ES) against fibrosis.
Methods: wild C5BL/6 and Balb/c mice, as well as the genetically modified strain TRPV1-/- were used. After a single dose of intratracheal bleomycin, the fibrotic response was analysed though histologic studies, the assessment of proinflammatory markers, myeloperoxidase activity, hydroxyproline content, genetic expression of VIP, PACAP, IL-1 β, IL-6, TNF-α and IL-11, as well as MAPK route (phospho-JNK, phospho-ERK), NF-κB (p-IκBα), β-cathenin, TGF-β (GSK-3B), SMAD (p-SMAD2) and pSTAT3, at a protein level.
Results: pulmonary fibrosis was more severe in TRPV1-/- mice compared to C5BL/6 mice. A significant increase in proinflammatory markers such as TNF-α, IL-1β, IL11 and IL-6, but not VIP or PACAP, was observed. pIKBα, pSTAT3, pSMAD2 and pJNK, but not pERK, were increased at a protein level in TRPV-/- mice.
Conclusions: the murine model of bleomycin-induced lung fibrosis remains a keystone to pioneer current investigation in lung fibrosis. Modulation of the ES might have a protective role.