Other studies investigating apoptosis related factors in COPD have shown that plasma levels of soluble Fas, an inhibitor of apoptosis, are only increased selleck bio in patients with severe COPD, while plasma levels of the inducer of Inhibitors,Modulators,Libraries apoptosis, sFasL, appear unchanged with disease severity. Since the transcription factor NF B controls the expres sion of many inflammatory and apoptotic genes, it is of particular interest in a disease such as COPD where neutrophil inflammation persists. The activated form of NF B is a heterodimer, usually made up of 2 Rel family proteins, p65 and p50 subunits. In unstim ulated cells NF B is sequestered in the cytoplasm due to its binding to I B and I B .
Following cell stimulation, I B is rapidly phosphorylated by specific protein kinases leading to proteolytic degradation and allowing NF B to translocate to the cell nucleus where it Inhibitors,Modulators,Libraries binds to specific B recognition elements in the promoter region of target genes. Studies investigating NF B expression in COPD subjects provide evidence for an increase in NF B translocation in lung tissue and sputum from COPD subjects compared to non smoking controls, which appears to be associated with an exacerbation. A recent study, described how a number of transcrip tion factors, including NF B, are overexpressed in bron chial epithelium from smokers with COPD. In order to elucidate the degree Inhibitors,Modulators,Libraries of constitutive neutrophil apoptosis in the inflammatory airways of COPD subjects and the potential involvement of NF B in this process we used three methods to investigate neutrophil Inhibitors,Modulators,Libraries apoptosis in COPD and determine any associated increase in NF B activation in airway neutrophils.
We hypothesised that there is a delay in neutrophil apoptosis Inhibitors,Modulators,Libraries in COPD subjects that is mediated, in part, by NF B binding in neutrophils. Methods Patients Age matched stable COPD patients, healthy con trol smokers and control non smokers were included in the study. COPD subjects had a history consistent with COPD as described in the British Thoracic Society guidelines. Inclusion criteria for stable COPD subjects were as fol lows no exacerbation within the preceding 4 weeks, over 50 years. 20 packyear history of smoking. FEV1 70% predicted, FEV1 FVC ratio 70% and 15% reversibility in response to 2 agonists. They were receiving treatment with anticholinergic, 2 agonists and or steroids. Exclu sion criteria were long term oral corticosteroids.
lung neoplasm and other serious concomitant disease. Control healthy smokers were over 50 years and 20 packyear inhibitor supplier history of smoking. control non smokers. Both control groups had normal lung function and sub jects were excluded if there was evidence of atopy asthma, chest disease, recent respiratory tract infection or antibi otic steroid treatment. The Queens University Belfast Research Ethics Committee approved the study.
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