Pahl Andreas, Szelenyi Stefan, Brune Kay
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuernberg, Erlangen, Germany.
ALTEX. 2006;23(2):59-63.
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.
慢性鼻-鼻窦炎（CRS）被定义为一种累及鼻窦和鼻道内衬的炎症性疾病，病程持续超过12周。它是当今最常见的慢性疾病之一，在西方世界影响着高达15%的成年人口，患病率急剧上升。CRS慢性炎症的一个标志是炎症组织中嗜酸性粒细胞和T淋巴细胞占主导地位。我们探讨了这样一个假说，即鼻窦阻塞会导致缺氧状态，进而诱导趋化活性，吸引炎症细胞。为此，我们通过证明缺氧能够诱导鼻上皮细胞释放趋化因子，建立了一个体外模型。此外，我们表明这种诱导会导致嗜酸性粒细胞和中性粒细胞的迁移。最后，我们通过展示其对临床使用的糖皮质激素地塞米松的敏感性，证明了这个体外模型的适用性。这些结果表明，这种鼻上皮细胞培养模型可能允许在体外直接在相关靶细胞上评估用于治疗CRS的新型抗炎化合物。这种方法可能会在CRS新疗法的筛选中取代并优化动物实验。
