ASK1 inhibition reduced elastase-induced pulmonary emphysema in mice

Chronic obstructive pulmonary disease (COPD) is considered the third leading cause of death by the World Health Organization. The most severe form of COPD is pulmonary emphysema, characterized by destruction of the alveolar parenchyma and consequent enlargement of the air spaces distal to the terminal bronchioles. Pulmonary emphysema still does not have an effective treatment, despite advances in the characterization of its pathophysiology. ASK1, apoptosis signal regulatory kinase 1, belongs to the MAPK family participating in inflammatory pathways involving p38 and JNK. The participation of ASK1 has been demonstrated in models of lung inflammation by LPS, bleomycin and lung injury induced by mechanical ventilation. However, no study was able to identify the participation of ASK1 in pulmonary emphysema until now. Here we investigated experimental treatment with selonsertib, an ASK1 inhibitor, in mice induced to emphysema by intratracheal instillation of elastase.