BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that mediates proinflammatory gene expression. NF-kappaB is activated when its inhibitor, IkappaBalpha, is phosphorylated and degraded. OBJECTIVES: The aims of this study were to compare the number of phosphorylated IkappaBalpha-immunopositive airway epithelial cells (AECs) in the peripheral airways of patients with COPD, asymptomatic smokers and asymptomatic nonsmokers. METHODS: We examined lung tissues obtained from 10 smokers with COPD, 7 asymptomatic smokers and 10 asymptomatic nonsmokers. Paraffin-embedded sections and immunohistochemical techniques were used to assess the number of phosphorylated IkappaBalpha-positive AECs as well as the numbers of tumor necrosis factor (TNF)alpha-positive, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive and 4-hydroxy-2-nonenal (4-HNE)-positive AECs in the peripheral airway specimens. RESULTS: The percentages of phosphorylated IkappaBalpha-positive AECs and TNFalpha-positive AECs out of the total number of AECs were significantly higher in patients with COPD than in asymptomatic nonsmokers (p < 0.05). The percentage of phosphorylated IkappaBalpha-positive AECs was positively correlated with the percentage of TNFalpha-positive AECs (r = 0.82, p < 0.01), but not with the percentage of 8-OHdG-positive AECs or the percentage of 4-HNE-positive AECs. CONCLUSIONS: The activation of NF-kappaB, which was evaluated by measuring the level of phosphorylated IkappaBalpha, was enhanced in the peripheral airway epithelia of the COPD patients in this study. The activation of NF-kappaB in the peripheral airway epithelium is associated with an elevated level of TNFalpha and seems to occur through a mechanism independent of oxidative stress.
BACKGROUND:Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that mediates proinflammatory gene expression. NF-kappaB is activated when its inhibitor, IkappaBalpha, is phosphorylated and degraded. OBJECTIVES: The aims of this study were to compare the number of phosphorylated IkappaBalpha-immunopositive airway epithelial cells (AECs) in the peripheral airways of patients with COPD, asymptomatic smokers and asymptomatic nonsmokers. METHODS: We examined lung tissues obtained from 10 smokers with COPD, 7 asymptomatic smokers and 10 asymptomatic nonsmokers. Paraffin-embedded sections and immunohistochemical techniques were used to assess the number of phosphorylated IkappaBalpha-positive AECs as well as the numbers of tumor necrosis factor (TNF)alpha-positive, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive and 4-hydroxy-2-nonenal (4-HNE)-positive AECs in the peripheral airway specimens. RESULTS: The percentages of phosphorylated IkappaBalpha-positive AECs and TNFalpha-positive AECs out of the total number of AECs were significantly higher in patients with COPD than in asymptomatic nonsmokers (p < 0.05). The percentage of phosphorylated IkappaBalpha-positive AECs was positively correlated with the percentage of TNFalpha-positive AECs (r = 0.82, p < 0.01), but not with the percentage of 8-OHdG-positive AECs or the percentage of 4-HNE-positive AECs. CONCLUSIONS: The activation of NF-kappaB, which was evaluated by measuring the level of phosphorylated IkappaBalpha, was enhanced in the peripheral airway epithelia of the COPDpatients in this study. The activation of NF-kappaB in the peripheral airway epithelium is associated with an elevated level of TNFalpha and seems to occur through a mechanism independent of oxidative stress.
Authors: R B Gonçalves; R D Coletta; K G Silvério; L Benevides; M Z Casati; J S da Silva; F H Nociti Journal: Inflamm Res Date: 2011-02-05 Impact factor: 4.575
Authors: Gimano D Amatngalim; Jasmijn A Schrumpf; Almira Henic; Esther Dronkers; Renate M Verhoosel; Soledad R Ordonez; Henk P Haagsman; Maria E Fuentes; Sriram Sridhar; Jamil Aarbiou; Richard A J Janssen; Annemarie N Lekkerkerker; Pieter S Hiemstra Journal: J Innate Immun Date: 2017-02-08 Impact factor: 7.349
Authors: Kohei Hasegawa; Marcos Pérez-Losada; Claire E Hoptay; Samuel Epstein; Jonathan M Mansbach; Stephen J Teach; Pedro A Piedra; Carlos A Camargo; Robert J Freishtat Journal: Pediatr Res Date: 2018-01-17 Impact factor: 3.756