文摘
The C-X-C motif chemokine 10 (CXCL10) or interferon gamma-induced protein 10 (IP-10) is a pro-inflammatory cytokine which has been attributed to many roles including cellular activation and migration. The activity of this cytokine is mediated by binding to the CXCR3 receptor primarily on T cells, natural killer cells, macrophages and also neutrophils. IP-10 is produced by a wide variety of inflammatory cells and also airway epithelia. Previous work has shown that increased levels of IP-10 are present in bronchoalveolar lavage fluid from patients with CF. In this study, we evaluated IP-10 levels in CF pulmonary epithelial cells and found that IP-10 expression and production were significantly increased in CF tracheal and bronchial epithelial cell lines compared to non-CF controls. The transcription factor IRF-1 has been reported to play a role in the regulation of IP-10 and our recent work has shown that IRF-1 levels are increased in CF pulmonary epithelial cells via dysregulation of the miRNA, miR-31. In agreement with previous work, knockdown of IRF-1 using siRNA significantly decreased expression and secretion of IP-10 from CF bronchial epithelial cells. In addition, overexpression of miR-31 in CF bronchial epithelial cells resulted in a decrease in the levels of IRF-1, which was also associated with a significant decrease in the expression and production of IP-10. These findings suggest that pulmonary epithelial cells may be a potential source of IP-10 in the CF lung via dysregulated miR-31. Further work is required to elucidate the role of elevated IP-10 in the pathogenesis of CF lung disease.