CD8(+) Tc-lymphocytes immunodeviation in peripheral blood and airway from patients of chronic obstructive pulmonary disease and changes after short-term smoking cessation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cigarette smoke induces an acute but persisting inflammation in peripheral blood and airway in chronic obstructive pulmonary disease (COPD), and CD8(+) Tc-lymphocytes are considered as a key role in this process. We aimed to investigate the Tc-lymphocytes immunodeviation in system and local airway of COPD patients and changes of the immunodeviation after short-term smoking cessation.</p><p><b>METHODS</b>Peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were collected from 42 patients (14 COPD patients, 16 smokers with normal lung function and 12 nonsmokers), while PB and induced sputum (IS) were obtained from other 19 patients (10 quitting smokers and 9 continuing smokers) at baseline and follow-up respectively of 4-week smoking cessation. Percentages of CD8(+) Tc-lymphocytes (%CD3(+)) and Tc1/Tc2 ratios were measured by flow cytometry.</p><p><b>RESULTS</b>Percentages of CD8(+) Tc-lymphocytes were higher in COPD patients than those in smokers and nonsmokers in both PB and BALF. Tc1/Tc2 ratio in PB and in BALF from COPD patients was greater than that from smokers and nonsmokers and negatively correlated with FEV1 %pre. When comparing the ratios between PB and BALF, significantly positive correlation was found in COPD patients. Furthermore, after 4-week smoking cessation, percentages of CD8(+) Tc-lymphocytes in PB and IS in quitting smokers were decreased compared to that in baseline and continuing smokers, whereas Tc1/Tc2 ratios were not influenced.</p><p><b>CONCLUSIONS</b>CD8(+) Tc1-trend immunodeviation profiles occurred in both system and local airway of COPD patients. This exceptional immunodeviation could not be relieved by short-term smoking cessation.</p>

ERK1/2 Promotes cigarette smoke-induced rat pulmonary artery smooth muscle cells proliferation and pulmonary vascular remodeling via up-regulating cycline1 expression / 华中科技大学学报（医学）（英德文版）

This study investigated the potential role of ERK1/2-cyclinE1 signaling pathway in rat pulmonary artery smooth muscle cells (rPASMCs) proliferation and pulmonary vascular remodeling induced by cigarette smoke exposure. A total of 24 male Wistar rats were randomly divided into 4 groups: control group (C group), S-1M, S-3M and S-6M groups (animals in the groups were exposed to smoke for 1, 3, and 6 months, respectively). HE staining and anti-α-smooth muscle actin antibody staining were performed to observe the degree of pulmonary vascular remodeling. Immunohistochemistry and Western blotting were performed to evaluate ERK1/2 and cyclinE1 expression in pulmonary vessels. Primary cultured rat pulmonary artery smooth muscle cells (rPASMCs) were exposed to cigarette smoke extract (CSE). ERK inhibitor (PD98059) and cyclinE1 siRNA were used to verify the role of ERK1/2 and cyclinE1 in CSE-induced rPASMCs proliferation. Cell proliferation was assessed by cell counting and 5-bromo-2-deoxyuridine (BrdU) incorporation. Our results showed that abnormal pulmonary vascular remodeling was found in cigarette smoked rats. Compared to C group, activated ERK1/2 and cyclinE1 expression was significantly increased in smoke-exposure groups. This up-regulated expression was positively correlated with the severity of pulmonary vascular remodeling, and there was positive correlation between the expression of ERK1/2 and cyclinE1. PD98059 and cyclinE1 siRNA inhibited the proliferation of rPASMCs. The expression of cyclinE1 could be down-regulated by PD98059. Our data demonstrated that increased expression of ERK1/2 and cyclinE1 might be involved in the pathogenesis of abnormal rPASMCs proliferation and rat pulmonary vascular remodelling induced by cigarette smoke exposure.

ERK1/2 promotes cigarette smoke-induced rat pulmonary artery smooth muscle cells proliferation and pulmonary vascular remodeling via up-regulating cycline1 expression / 华中科技大学学报（医学）（英德文版）

This study investigated the potential role of ERK1/2-cyclinE1 signaling pathway in rat pulmonary artery smooth muscle cells (rPASMCs) proliferation and pulmonary vascular remodeling induced by cigarette smoke exposure. A total of 24 male Wistar rats were randomly divided into 4 groups: control group (C group), S-1M, S-3M and S-6M groups (animals in the groups were exposed to smoke for 1, 3, and 6 months, respectively). HE staining and anti-α-smooth muscle actin antibody staining were performed to observe the degree of pulmonary vascular remodeling. Immunohistochemistry and Western blotting were performed to evaluate ERK1/2 and cyclinE1 expression in pulmonary vessels. Primary cultured rat pulmonary artery smooth muscle cells (rPASMCs) were exposed to cigarette smoke extract (CSE). ERK inhibitor (PD98059) and cyclinE1 siRNA were used to verify the role of ERK1/2 and cyclinE1 in CSE-induced rPASMCs proliferation. Cell proliferation was assessed by cell counting and 5-bromo-2-deoxyuridine (BrdU) incorporation. Our results showed that abnormal pulmonary vascular remodeling was found in cigarette smoked rats. Compared to C group, activated ERK1/2 and cyclinE1 expression was significantly increased in smoke-exposure groups. This up-regulated expression was positively correlated with the severity of pulmonary vascular remodeling, and there was positive correlation between the expression of ERK1/2 and cyclinE1. PD98059 and cyclinE1 siRNA inhibited the proliferation of rPASMCs. The expression of cyclinE1 could be down-regulated by PD98059. Our data demonstrated that increased expression of ERK1/2 and cyclinE1 might be involved in the pathogenesis of abnormal rPASMCs proliferation and rat pulmonary vascular remodelling induced by cigarette smoke exposure.