EXPLORING SPECIFIC P38α ACTIVATION AND ITS EFFECT ON LUNG PHYSIOLOGY AND PATHOLOGY

Abstract

The MAP kinase (MAPK) p38α is a key component in the acute inflammatory response, and its upregulated activity has been consistently observed in possibly all chronic inflammatory diseases. Nonetheless, its contributions to disease are less straightforward than initially expected, with p38α inhibitors proving unsuccessful thus far. To elucidate the specific outcomes of p38α activation from its complex signalling networks, we developed novel transgenic mouse models capable of activating p38α alone in a controllable manner. The outcomes of specific p38α activation can thus be observed in vivo for the first time. We placed particular emphasis on the lungs in this research as p38α is a central component in pathologies such as asthma and chronic obstructive pulmonary disease (COPD). The insights derived from these mouse models can hopefully inform more efficacious strategies to therapeutically modulate p38α signalling for the treatment of chronic respiratory diseases in the future.