Role of fibroblast for eosinophilic airway inflammation

鼻息肉病和哮喘都是气道炎性疾病的表现。在这两种情况下，基质异常，如纤维化、基底膜增厚、上皮脱落伴上皮化生，都在不同程度上得到了很好的描述。成纤维细胞是细胞因子、炎症细胞因子和炎症介质的丰富来源，被认为在纤维化的发展中起重要作用。此外，有相当多的证据表明嗜酸性粒细胞参与鼻息肉和哮喘的病理生理。虽然鼻息肉和哮喘中嗜酸性粒细胞数量增加，但其选择性积累的机制尚不完全清楚。RANTES和eotaxin是促进嗜酸性粒细胞募集的趋化因子。因此，这些可能是鼻息肉和哮喘中嗜酸性粒细胞募集的重要分子。利用原代气道组织源性成纤维细胞系，我们发现IL-1和TNF诱导气道成纤维细胞中RANTES和eotaxin的基因表达和蛋白产生，LPS仅诱导鼻腔成纤维细胞中RANTES的基因表达和蛋白产生，而在咽、气管、支气管和肺成纤维细胞中没有。这些数据提示，气道成纤维细胞可能在气道疾病中嗜酸性粒细胞的募集中发挥重要作用。

Nasal polyposis and asthma are both manifestations of airway inflammatory diseases. Stromal abnormalities such as fibrosis, thickening of the basement membrane, and slughed-off epithelium with areas of epithelial metaplasia have been well described in varying degree, in both conditions. Fibroblasts are a rich source of cytokines and inflammatory cytokines and inflammatory mediators and are thought to play an important role in the development of fibrosis. In addition, there is considerable evidence for the participation of eosinophils in the pathophysiology of nasal polyps and asthma. Although increased numbers of eosinophils are present in nasal polyps and asthma, the mechanisms responsible for their selective accumulation are not completely clear. RANTES and eotaxin are chemokines that promote the recruitment of eosinophils. Thus, those may be important molecules for the recruitment of eosinophils in nasal polyps and asthma. Using primary airway tissue-derived fibroblast lines, we demonstrate that IL-1 and TNF induced the gene expression and protein production of RANTES and eotaxin in airway fibroblasts, and that LPS induced the gene expression and production of RANTES only in nasal but not in pharyngeal, tracheal, bronchial, and lung fibroblasts. These data suggest that airway fibroblasts may play an important role in the recruitment of eosinophils in airway diseases.