NOVEL STRATEGIES TO TREAT DETRIMENTAL AIRWAY INFLAMMATION

Chronic airway inflammation results in tissue damage and remodeling (fibrosis). Mechanisms regulating influx of immune cells to the airways and their activation are of major importance.

In the project, novel treatment strategies against asthma and COPD, having higher precision and less side-effects will be identified. Furthermore, we will investigate effects of these treatments in models of idiopathic pulmonary fibrosis (IPF).

In particular:Reducing inflammation and fibrosis through pharmacological inhibition of  enzymes excising oxidized guanines (OGG1 and MTH1).

OGG1 promotes activity of the proinflammatory transcription factor NF-kB while MTH1 is highly expressed in activated T cells.

In models of airway inflammation and fibrosis, we will investigate the effects from inhibition of OGG1 and MTH1 on cell recruitment, mucus-production, and airway remodeling (i.e. fibrosis).Targeting Tartrate-Resistant Acid Phosphatase 5 (TRAP5) to reduce inflammation.

We have shown that TRAP5 is essential for macrophages and neutrophil recruitment to the airways during airway inflammation and fibrosis.

The mechanisms involved and possible pharmaceutical targeting of TRAP5 will be further investigated.In the project, we apply in vivo and ex vivo models of airway inflammation and fibrosis as well as investigation of patient samples.

The strategies mentioned above can serve as templates for novel pharmaceutical treatments, reducing the need for corticosteroids that have severe side-effects.