This relevant for CF as CFTR dysfunction has been shown to affect cellular cholesterol and SREBP. Furthermore, alterations in cellular cholesterol may play a role in the inflammatory phenotype in CF. The goal of this study was to analyze if decreased CFTR expression in human AM affects inflammation and apoptosis by using unstimulated AM derived from non-CF subjects with silenced CFTR expression; to focus on Cav 1 and its regulation by SREBP as a potential factor. We found that silencing of CFTR induced an inflammatory phenotype and augmented apoptosis that were at least partially regulated by SREBP-mediated Cav1 expression. These findings suggest that defective CFTR in AM is relevant for the inflammation in CF lung disease. The contribution of AM to the hyperinflammatory milieu in the CF lung is not clear. The present study attempts to address this question by analyzing AM from healthy donors in which expression of CFTR is decreased by siRNA-mediated knockdown. AM with decreased CFTR expression exhibited an inflammatory phenotype as evidence by increased IL-8 and NF-kB, similar to the phenotype described in epithelial cells that express no or defective CFTR. In contrast to data obtained in epithelial cells, our results demonstrated an inverse relationship between expression of CFTR and apoptosis as well as expression of mSREBP. The data suggest an AM specific phenotype in which increased expression of Cav1 could be a consequence of decreased mSREBP and cause for increased apoptosis in this cell type. A hyperinflammatory response is a hallmark of CF lung disease. Oritavancin CFTR-deficient epithelial cells or epithelial cells Sinapine-thiocyanate treated with CFTR chloride channel inhibitors show increased secretion of IL8. Elevated levels of proinflammatory cytokines, such as IL-8 and IL-6, and decreased levels of the anti-inflammatory cytokine IL-10 are characteristic findings in the bronchioalveolar lavage fluid of CF patients even in the absence of pathogens.These cytokines are thought to be primarily produced by the CFTR-deficient epithelial cells, however increased baseline levels of IL-8 have also been observed in blood monocytes of CF patients and in AM derived from CF knockout mice.