Impairment of Immunoproteasome Function by Cigarette Smoke and in Chronic Obstructive Pulmonary Diseaseстатья из журнала
Аннотация: Patients with chronic obstructive pulmonary disease (COPD) and in particular smokers are more susceptible to respiratory infections contributing to acute exacerbations of disease. The immunoproteasome is a specialized type of proteasome destined to improve major histocompatibility complex (MHC) class I-mediated antigen presentation for the resolution of intracellular infections.To characterize immunoproteasome function in COPD and its regulation by cigarette smoke.Immunoproteasome expression and activity were determined in bronchoalveolar lavage (BAL) and lungs of human donors and patients with COPD or idiopathic pulmonary fibrosis (IPF), as well as in cigarette smoke-exposed mice. Smoke-mediated alterations of immunoproteasome activity and MHC I surface expression were analyzed in human blood-derived macrophages. Immunoproteasome-specific MHC I antigen presentation was evaluated in spleen and lung immune cells that had been smoke-exposed in vitro or in vivo.Immunoproteasome and MHC I mRNA expression was reduced in BAL cells of patients with COPD and in isolated alveolar macrophages of patients with COPD or IPF. Exposure of immune cells to cigarette smoke extract in vitro reduced immunoproteasome activity and impaired immunoproteasome-specific MHC I antigen presentation. In vivo, acute cigarette smoke exposure dynamically regulated immunoproteasome function and MHC I antigen presentation in mouse BAL cells. End-stage COPD lungs showed markedly impaired immunoproteasome activities.We here show that the activity of the immunoproteasome is impaired by cigarette smoke resulting in reduced MHC I antigen presentation. Regulation of immunoproteasome function by cigarette smoke may thus alter adaptive immune responses and add to prolonged infections and exacerbations in COPD and IPF.
Год издания: 2016
Авторы: Ilona Kammerl, Angela Dann, Alessandra Mossina, Dorothee Brech, Christina Lukas, Oliver Vosyka, Petra Nathan, Thomas M. Conlon, Darcy E. Wagner, Herman S. Overkleeft, Antje Prasse, Iván O. Rosas, Tobias Straub, Susanne Krauss–Etschmann, Mélanie Königshoff, Gerhard Preißler, H. Winter, Michael Lindner, Rudolf Hatz, Jürgen Behr, Katharina Heinzelmann, Ali Önder Yildirim, Elfriede Noeßner, Oliver Eickelberg, Silke Meiners
Издательство: American Thoracic Society
Источник: American Journal of Respiratory and Critical Care Medicine
Ключевые слова: Ubiquitin and proteasome pathways, Peptidase Inhibition and Analysis, Protease and Inhibitor Mechanisms
Другие ссылки: American Journal of Respiratory and Critical Care Medicine (HTML)
PubMed (HTML)
PubMed (HTML)
Открытый доступ: closed
Том: 193
Выпуск: 11
Страницы: 1230–1241