tailieunhanh - Báo cáo y học: " Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury"

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:" Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury. | Zhou et al. Respiratory Research 2011 12 78 http content 12 1 78 RESPIRATORY RESEARCH RESEARCH Open Access Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury Fang Zhou1 Shigemitsu Onizawa2 Atsushi Nagai2 and Kazutetsu Aoshiba1 2 Abstract Background Genotoxic stress such as by exposure to bromodeoxyuridine BrdU and cigarette smoke induces premature cell senescence. Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients. However whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown. The present study was designed to test the hypothesis that premature senescence of airway epithelial cells Clara cells impairs repair processes and exacerbates inflammation after airway injury. Methods C57 BL6J mice were injected with the Clara-cell-specific toxicant naphthalene NA on days 0 7 and 14 and each NA injection was followed by a daily dose of BrdU on each of the following 3 days during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce. The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose. Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation. NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312. Human lung tissue samples were obtained from COPD patients asymptomatic smokers and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients and if so whether it is accompanied by p38 MAPK activation. Results BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure. However after repeated NA exposure BrdU induced epithelial cell Clara cell senescence as .