TRAIL-Dependent Resolution of Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necro...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/7934362 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832563467268128768 |
|---|---|
| author | David M. Habiel Ana Paula Moreira Ugur B. Ismailoglu Michael P. Dunleavy Karen A. Cavassani Nico van Rooijen Ana Lucia Coelho Cory M. Hogaboam |
| author_facet | David M. Habiel Ana Paula Moreira Ugur B. Ismailoglu Michael P. Dunleavy Karen A. Cavassani Nico van Rooijen Ana Lucia Coelho Cory M. Hogaboam |
| author_sort | David M. Habiel |
| collection | DOAJ |
| description | Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) was key to the resolution of bleomycin-induced pulmonary fibrosis. Both in vivo and in vitro studies demonstrated that Gr-1+TRAIL+ bone marrow-derived myeloid cells blocked the activation of lung myofibroblasts. Although soluble TRAIL was increased in plasma from IPF patients, the presence of TRAIL+ myeloid cells was markedly reduced in IPF lung biopsies, and primary lung fibroblasts from this patient group expressed little of the TRAIL receptor-2 (DR5) when compared with appropriate normal samples. IL-13 was a potent inhibitor of DR5 expression in normal fibroblasts. Together, these results identified TRAIL+ myeloid cells as a critical mechanism in the resolution of pulmonary fibrosis, and strategies directed at promoting its function might have therapeutic potential in IPF. |
| format | Article |
| id | doaj-art-f76588a1e5d54b619687aad86e227d6d |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-f76588a1e5d54b619687aad86e227d6d2025-02-03T01:20:14ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/79343627934362TRAIL-Dependent Resolution of Pulmonary FibrosisDavid M. Habiel0Ana Paula Moreira1Ugur B. Ismailoglu2Michael P. Dunleavy3Karen A. Cavassani4Nico van Rooijen5Ana Lucia Coelho6Cory M. Hogaboam7Women’s Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAImmunology Group, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48103, USAImmunology Group, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48103, USAImmunology Group, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48103, USAUrologic Oncology Program and Uro-Oncology Research Laboratories, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, Vrije Universiteit Medisch Centrum, 1081 BT Amsterdam, NetherlandsWomen’s Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAWomen’s Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAIdiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) was key to the resolution of bleomycin-induced pulmonary fibrosis. Both in vivo and in vitro studies demonstrated that Gr-1+TRAIL+ bone marrow-derived myeloid cells blocked the activation of lung myofibroblasts. Although soluble TRAIL was increased in plasma from IPF patients, the presence of TRAIL+ myeloid cells was markedly reduced in IPF lung biopsies, and primary lung fibroblasts from this patient group expressed little of the TRAIL receptor-2 (DR5) when compared with appropriate normal samples. IL-13 was a potent inhibitor of DR5 expression in normal fibroblasts. Together, these results identified TRAIL+ myeloid cells as a critical mechanism in the resolution of pulmonary fibrosis, and strategies directed at promoting its function might have therapeutic potential in IPF.http://dx.doi.org/10.1155/2018/7934362 |
| spellingShingle | David M. Habiel Ana Paula Moreira Ugur B. Ismailoglu Michael P. Dunleavy Karen A. Cavassani Nico van Rooijen Ana Lucia Coelho Cory M. Hogaboam TRAIL-Dependent Resolution of Pulmonary Fibrosis Mediators of Inflammation |
| title | TRAIL-Dependent Resolution of Pulmonary Fibrosis |
| title_full | TRAIL-Dependent Resolution of Pulmonary Fibrosis |
| title_fullStr | TRAIL-Dependent Resolution of Pulmonary Fibrosis |
| title_full_unstemmed | TRAIL-Dependent Resolution of Pulmonary Fibrosis |
| title_short | TRAIL-Dependent Resolution of Pulmonary Fibrosis |
| title_sort | trail dependent resolution of pulmonary fibrosis |
| url | http://dx.doi.org/10.1155/2018/7934362 |
| work_keys_str_mv | AT davidmhabiel traildependentresolutionofpulmonaryfibrosis AT anapaulamoreira traildependentresolutionofpulmonaryfibrosis AT ugurbismailoglu traildependentresolutionofpulmonaryfibrosis AT michaelpdunleavy traildependentresolutionofpulmonaryfibrosis AT karenacavassani traildependentresolutionofpulmonaryfibrosis AT nicovanrooijen traildependentresolutionofpulmonaryfibrosis AT analuciacoelho traildependentresolutionofpulmonaryfibrosis AT corymhogaboam traildependentresolutionofpulmonaryfibrosis |