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      Antibacterial Defense of Human Airway Epithelial Cells from Chronic Obstructive Pulmonary Disease Patients Induced by Acute Exposure to Nontypeable Haemophilus influenzae: Modulation by Cigarette Smoke

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          Abstract

          Antimicrobial proteins and peptides (AMPs) are a central component of the antibacterial activity of airway epithelial cells. It has been proposed that a decrease in antibacterial lung defense contributes to an increased susceptibility to microbial infection in smokers and patients with chronic obstructive pulmonary disease (COPD). However, whether reduced AMP expression in the epithelium contributes to this lower defense is largely unknown. We investigated the bacterial killing activity and expression of AMPs by air-liquid interface-cultured primary bronchial epithelial cells from COPD patients and non-COPD (ex-)smokers that were stimulated with nontypeable Haemophilus influenzae (NTHi). In addition, the effect of cigarette smoke on AMP expression and the activation of signaling pathways was determined. COPD cell cultures displayed reduced antibacterial activity, whereas smoke exposure suppressed the NTHi-induced expression of AMPs and further increased IL-8 expression in COPD and non-COPD cultures. Moreover, smoke exposure impaired NTHi-induced activation of NF-κB, but not MAP-kinase signaling. Our findings demonstrate that the antibacterial activity of cultured airway epithelial cells induced by acute bacterial exposure was reduced in COPD and suppressed by cigarette smoke, whereas inflammatory responses persisted. These findings help to explain the imbalance between protective antibacterial and destructive inflammatory innate immune responses in COPD.

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          Author and article information

          Journal
          J Innate Immun
          J Innate Immun
          JIN
          Journal of Innate Immunity
          S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH-4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )
          1662-811X
          1662-8128
          July 2017
          8 February 2017
          8 February 2017
          : 9
          : 4
          : 359-374
          Affiliations
          [1] aDepartment of Pulmonology, Leiden University Medical Center, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
          [2] bGalapagos BV, Leiden, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
          [3] cDepartment of Infectious Diseases and Immunology, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
          [4] dHoffmann La Roche, Nutley, NJ, USA
          Author notes
          *Dr. Gimano D. Amatngalim, Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, NL-2333 ZA Leiden (The Netherlands), E-Mail g.d.amatngalim@ 123456lumc.nl
          Article
          PMC5569706 PMC5569706 5569706 jin-0009-0359
          10.1159/000455193
          5569706
          28171878
          2a761920-0e39-4ceb-8031-5737dcceb69f
          Copyright © 2017 by S. Karger AG, Basel
          History
          : 16 March 2016
          : 19 December 2016
          Page count
          Figures: 8, Tables: 3, References: 56, Pages: 16
          Categories
          Research Article

          Antimicrobial peptides,Epithelium,Host defense,Chronic obstructive pulmonary disease,Cigarette smoke

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