Sökning: WFRF:(Jevnikar Z.) >
Lung macrophages dr...
Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis
-
- Andelid, Kristina, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
-
Ost, K. (författare)
-
- Andersson, Anders (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
-
visa fler...
-
Mohamed, E. (författare)
-
Jevnikar, Z. (författare)
-
- Vanfleteren, Lowie E G W (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
-
Goransson, M. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2021-06-07
- 2021
- Engelska.
-
Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 22:1
- Relaterad länk:
-
https://respiratory-...
-
visa fler...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Background: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. Methods: In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. Results: We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air-liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNF alpha in this cross-talk. Conclusions: For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNF alpha-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Nyckelord
- COPD
- Chronic bronchitis
- Sputum macrophages
- Steroid resistance
- TNF
- alpha
- MUC5B
- Macrophage-epithelial cross-talk
- goblet cell hyperplasia
- tnf-alpha
- bronchoalveolar lavage
- regression
- equations
- reference values
- function tests
- up-regulation
- major mucin
- sputum
- therapy
- Respiratory System
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas