Environmental triggers like cigarette smoke, respiratory viruses and house dust mite play an important role in the inception and exacerbation of asthma. In this thesis, we investigated the effects of these environmental triggers on airway epithelial cells. A special role in these studies was reserved for Pim1 kinase, a protein highly expressed in airway epithelial cells and involved in the survival of these cells. We demonstrated with in vivo and in vitro studies that Pim1 kinase plays a protective role in the airway epithelial cells exposed to cigarette smoke and house dust mite. With the studies on the human respiratory virus Rhinovirus, we showed that Pim1 kinase is involved in the replication of human rhinovirus in the airway epithelial cells. Interestingly, we observed that viral replication was significantly reduced by pharmacological inhibition of Pim1 kinase activity. These observations offer a new therapeutic approach against viral infections, which might be highly beneficial for asthma patients who frequently suffer from virally induced asthma exacerbations. Future research should reveal this potential of Pim1 kinase inhibitors as novel therapeutic targets and assess if the beneficial effects of reducing viral replication in airway epithelial cells will transcend the protective role of Pim1 kinase as observed in the studies with cigarette smoke and house dust mite.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2015|