Hypoxia induced chemokine expression in nasal epithelial cells: development of an in vitro model for chronic rhinosinusitis.
Chronic rhinosinusitis (CRS) is defined as an inflammatory condition involving the paranasal sinuses and the lining of the nasal passages that persists longer than 12 weeks. It is one of the most common chronic diseases today, affecting up to 15% of the adult population in the Western world with a dramatic increase in prevalence. One hallmark of chronic inflammation in CRS is the predominance of eosinophils and T lymphocytes in the inflamed tissue. We pursued the hypothesis that the blockage of the paranasal sinuses induces hypoxic conditions, which subsequently lead to the induction of chemotactic activity, attracting inflammatory cells. To this end, we established an in vitro model by showing that hypoxia is able to induce the release of chemokines in nasal epithelial cells. Furthermore, we show that this induction leads to the migration of eosinophils and neutrophils. Finally, we demonstrated the applicability of this in vitro model by showing its sensitivity to the glucocorticoid dexamethasone, which is used in the clinical situation. These results suggest that this nasal epithelial cell culture model may allow the evaluation of novel anti-inflammatory compounds for the treatment of CRS directly on the relevant target cells in vitro. This approach may result in replacing and refining animal experimentation in the screening of new therapeutics for CRS.
Pahl
Andreas
A
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuernberg, Erlangen, Germany. pahl@pharmakologie.uni-erlangen.de
Szelenyi
Stefan
S
Brune
Kay
K