Macrophage migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine sustaining the acute response to gram-negative bacteria and a regulatory role for MIF in Cystic Fibrosis has been suggested by the presence of a functional, polymorphic, four-nucleotide repeat in this gene's promoter at position -794, with the 5-repeat allele displaying lower promoter activity. We aimed at assessing the...

BACKGROUND Knowledge of how CFTR mutations other than F508del translate into the basic defect in cystic fibrosis (CF) is scarce due to the low incidence of homozygous index cases. METHODS 17 individuals who are homozygous for deletions, missense, stop or splice site mutations in the CFTR gene were investigated for clinical symptoms of CF and assessed in CFTR function by sweat test, nasal pote...

BACKGROUND High-dose ibuprofen is clinically effective in cystic fibrosis (CF); however, its molecular mechanisms are poorly understood. OBJECTIVE To test the hypothesis that clinically relevant concentrations of ibuprofen suppress activation of nuclear factor (NF)-kappaB and thus down-regulate stimulated interleukin (IL)-8 production in CF respiratory epithelial cells. METHODS The majority...

We optically measured effects of orally available ivacaftor (Kalydeco®) on sweat rates of identified glands in 3 R117H subjects, each having a unique set of additional mutations, and compared them with 5 healthy control subjects tested contemporaneously. We injected β-adrenergic agonists intradermally to stimulate CFTR-dependent 'C-sweat' and methacholine to stimulate 'M-sweat', which persists ...

Cystic fibrosis (CF) is the most frequent lethal genetic disorder among Caucasians. It depends on alterations of a chloride channel expressed by most epithelial cells and encoded by CFTR gene. Also using scanning techniques to analyze the whole coding regions of CFTR gene, mutations are not identified in up to 10% of CF alleles, and such figure increases in CFTR-related disorders (CFTR-RD). Oth...

Cystic fibrosis (CF) is a lethal genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite recent groundbreaking approval of genotype-specific small-molecule drugs, a significant portion of CF patients still lack effective therapeutic options that address the underlying cause of the disease. Through a phenotypic high-throughput screen of...

Background: High-dose ibuprofen is clinically effective in cystic fibrosis (CF); however, its molecular mechanisms are poorly understood. Objective: To test the hypothesis that clinically relevant concentrations of ibuprofen suppress activation of nuclear factor (NF)B and thus down-regulate stimulated interleukin (IL)-8 production in CF respiratory epithelial cells. Methods: The majority of exp...

Objectives: Cystic fibrosis is caused by a variant in the cystic transmembrane conductance regulator protein, of which class II variant, F508del, commonest. A number therapies aiming to correct F508del defect have been assessed clinical trials using change FEV1 and sweat chloride as outcome measures. We aim establish if there correlation between changes studies included Cochrane systematic revi...

Ahner A, Gong X, Frizzell RA. Divergent signaling via SUMO modification: potential for CFTR modulation. Am J Physiol Cell Physiol 310: C175–C180, 2016; doi:10.1152/ajpcell.00124.2015.—The cystic fibrosis transmembrane conductance regulator (CFTR) is generally responsible for the cAMP/PKA regulated anion conductance at the apical membranes of secretory epithelial cells. Mutations in CFTR underli...