MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells
MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells
复制标题
DOI：
10.1165/rcmb.2006-0200oc
复制
发表时间：
2007-05-01
影响因子：
6.4
通讯作者：
Cabrini, Giulio
中科院分区：
文献类型：
--
作者：
Dechecchi, Maria Cristina;Nicolis, Elena;Cabrini, Giulio
囊性纤维化（CF）慢性肺炎症的具体特征是支气管内中性粒细胞浸润为主，铜绿假单胞菌定植，细胞因子和趋化因子水平升高，首先是IL-8。CF肺中广泛的炎症过程是进行性组织损伤的基础，并且在很大程度上被认为是有害的，因此抗炎方法是相关的治疗靶点。这种中性粒细胞主导的炎症似乎与过度的促炎信号有关，起源于表达有缺陷的CIF跨膜传导调节（CFTR）蛋白的相同表面上皮细胞，尽管其潜在机制尚未完全阐明。为了研究CFTR缺陷与CIF气道细胞对P. aeruginosa的炎症反应之间的关系，我们研究了Delta F508 CFTR纠正剂benzo(c)quinolizinium (MPB)-07的作用（Dormer et al., J Cell Science 2001;114:4073-4081）。与野生型、表达cfr的支气管细胞、S9和NuLi-1细胞相比，CIF支气管上皮IB3-1和CuFi-1细胞对P. aeruginosa的反应过量产生炎症分子、IL-8和细胞间粘附分子(ICAM)-1。在IB3-1和CuFi-1细胞中，校正者MPB-07显著降低铜绿假单胞菌感染引起的IL-8和ICAM-1 mRNA的表达。mpb -07处理的IB3-1和CuFi-1细胞证实cftr依赖性Cl-外排得到纠正。综上所述，Delta F508 CFTR校正剂MPB-07在体外暴露于铜绿假单胞菌的CIF支气管细胞中具有抗炎作用。
Chronic lung inflammation in cystic fibrosis (CF) is specifically characterized by predominant endobronchial neutrophil infiltrates, colonization by Pseudomonas aeruginosa, and elevated levels of cytokines and chemokines, first of all IL-8. The extensive inflammatory process in CF lungs is the basis of progressive tissue damage and is largely considered detrimental, making antiinflammatory approaches a relevant therapeutic target. This neutrophil-dominated inflammation seems to be related to an excessive proinflammatory signaling, originating from the same surface epithelial cells expressing the defective CIF transmembrane conductance regulator (CFTR) protein, although the underlying mechanisms have not been completely elucidated. To investigate the relationship between defective CFTR and the inflammatory response to P. aeruginosa in CIF airway cells, we studied the effect of the Delta F508 CFTR corrector, benzo(c)quinolizinium (MPB)-07 (Dormer et al., J Cell Science 2001;114:4073-4081). CIF bronchial epithelial IB3-1 and CuFi-1 cells overproduced the inflammatory molecules, IL-8 and intercellular adhesion molecule (ICAM)-1, in response to P. aeruginosa, compared with the wild-type, CFTR-expressing bronchial cells, S9, and NuLi-1 cells. In both IB3-1 and CuFi-1 cells, the corrector MPB-07 dramatically reduces the IL-8 and ICAM-1 mRNA expression elicited by P. aeruginosa infection. Correction of CFTR-dependent Cl- efflux was confirmed in MPB-07-treated IB3-1 and CuFi-1 cells. In conclusion, the Delta F508 CFTR corrector MPB-07 produces an antiinflammatory effect in CIF bronchial cells exposed to P. aeruginosa in vitro.