Zeguang Zheng1, Yafei Qi1,2, Xiaoming Xu1, Hua Jiang1, Zhengtu Li1, Quan Yang1, Chenting Zhang1, Kedong Zhang1, Rongchang Chen1, Jian Wang1, Wenju Lu1,3. 1. State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China. 2. Central Hospital of Panyu District, Guangzhou 511470, China. 3. Department of Laboratory Medicine, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
Abstract
BACKGROUND: Mucin 1 (MUC1) is a membrane tethered protein on airway epithelial cells. This protein is upregulated and plays an important anti-inflammatory role during acute lung inflammation. However, the relationship between sputum MUC1 level and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unknown. METHODS: The levels of MUC1, IL-8, and TNF-α in induced sputum from 78 COPD patients were assessed by ELISA. The association between COPD exacerbation and MUC1 fragment levels was analyzed. An acute airway inflammation mouse model was established by intranasal LPS inhalation. The expression of Muc1 in lung and the levels of Muc1, TNF-α and KC in BAL fluid from mice were determined with western blotting and ELISA, respectively. RESULTS: Higher levels of MUC1 membrane-tethered (CT) and extracellular (EC) fragments, cytokines TNF-α and IL-8, more leucocyte and neutrophil counts were found in sputum from COPD patients in acute than in remission phase. Linear regression analysis confirmed that the level of sputum MUC1 CT fragment is positively correlated with sputum neutrophil number and patients' age; whereas the sputum EC fragment level is correlated inversely with FEV1/FVC value and positively with patients' age. Inhalation of lipopolysaccharide (LPS) induced acute lung inflammation in mice which exhibited increased levels of Muc1 CT fragment in lung and only Muc1 EC fragment increase in BAL fluid. CONCLUSIONS: Unlike pure bacterial induced lung inflammation, both sputum MUC1 CT and EC fragments are increased during acute exacerbation of COPD. The clinical benefits from measuring the changes of various sputum MUC1 fragments in AECOPD need to be elucidated in future studies.
BACKGROUND:Mucin 1 (MUC1) is a membrane tethered protein on airway epithelial cells. This protein is upregulated and plays an important anti-inflammatory role during acute lung inflammation. However, the relationship between sputum MUC1 level and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unknown. METHODS: The levels of MUC1, IL-8, and TNF-α in induced sputum from 78 COPDpatients were assessed by ELISA. The association between COPD exacerbation and MUC1 fragment levels was analyzed. An acute airway inflammationmouse model was established by intranasal LPS inhalation. The expression of Muc1 in lung and the levels of Muc1, TNF-α and KC in BAL fluid from mice were determined with western blotting and ELISA, respectively. RESULTS: Higher levels of MUC1 membrane-tethered (CT) and extracellular (EC) fragments, cytokines TNF-α and IL-8, more leucocyte and neutrophil counts were found in sputum from COPDpatients in acute than in remission phase. Linear regression analysis confirmed that the level of sputum MUC1 CT fragment is positively correlated with sputum neutrophil number and patients' age; whereas the sputum EC fragment level is correlated inversely with FEV1/FVC value and positively with patients' age. Inhalation of lipopolysaccharide (LPS) induced acute lung inflammation in mice which exhibited increased levels of Muc1 CT fragment in lung and only Muc1 EC fragment increase in BAL fluid. CONCLUSIONS: Unlike pure bacterial induced lung inflammation, both sputum MUC1 CT and EC fragments are increased during acute exacerbation of COPD. The clinical benefits from measuring the changes of various sputum MUC1 fragments in AECOPD need to be elucidated in future studies.
Authors: Min-Jong Kang; Je-Min Choi; Bo Hye Kim; Chang-Min Lee; Won-Kyung Cho; Gina Choe; Do-Hyun Kim; Chun Geun Lee; Jack A Elias Journal: Am J Respir Crit Care Med Date: 2012-03-01 Impact factor: 21.405
Authors: Fanny W S Ko; Margaret Ip; Paul K S Chan; Joan P C Fok; Michael C H Chan; Jenny C Ngai; Doris P S Chan; David S C Hui Journal: Chest Date: 2007-01 Impact factor: 9.410
Authors: E Pizzichini; M M Pizzichini; A Efthimiadis; S Evans; M M Morris; D Squillace; G J Gleich; J Dolovich; F E Hargreave Journal: Am J Respir Crit Care Med Date: 1996-08 Impact factor: 21.405
Authors: Heta Merikallio; Riitta Kaarteenaho; Sara Lindén; Médea Padra; Reza Karimi; Chuan-Xing Li; Elisa Lappi-Blanco; Åsa M Wheelock; Magnus C Sköld Journal: Respir Res Date: 2020-09-18