Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: "Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD. | Heijink et al. Respiratory Research 2011 12 110 http content 12 1 110 RESPIRATORY RESEARCH RESEARCH Open Access Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD 1 12 2 Irene H Heijink 1 Simone M Brandenburg Jacobien A Noordhoek Dirk-Jan Slebos Dirkje S Postma and Antoon J van Oosterhout1 Abstract Background Cigarette smoke the major risk factor for COPD is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases particularly A Disintegrin and Metalloproteinase ADAM 17 contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-a cytokines implicated in COPD pathogenesis. Methods We studied the effects of cigarette smoke extract CSE and metalloproteinase inhibitors on TGF-a and IL-8 release in primary bronchial epithelial cells PBECs from COPD patients healthy smokers and non-smokers. Results We observed that TGF-a was mainly shed by ADAM17 in PBECs from all groups. Interestingly IL-8 production occurred independently from ADAM17 and TGF-a shedding but was significantly inhibited by broadspectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-a shedding while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase TIMP -3 levels suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore whereas baseline TGF-a shedding was lower in COPD PBECs the early release of IL-8 likely due to its shedding was higher in PBECs from COPD than healthy smokers. Importantly this was accompanied by lower TIMP-2 levels in COPD PBECs while baseline TIMP-3 levels were similar between groups. Conclusions Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-a shedding and that .
