Publications
Detailed Information
Natural killer T (NKT) cells attenuate bleomycin-induced pulmonary fibrosis by producing interferon-gamma
Cited 0 time in
Web of Science
Cited 0 time in Scopus
- Authors
- Issue Date
- 2005-10-28
- Citation
- Am J Pathol 2005, 167:1231-1241
- Keywords
- Adoptive Transfer ; Animals ; Bleomycin ; Body Weight ; Cells, Cultured ; Disease Models, Animal ; Hydroxyproline/analysis ; Interferon-gamma/*biosynthesis/genetics ; Killer Cells, Natural/*immunology ; Lung/drug effects/*pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Fibrosis/chemically induced/*immunology/*pathology ; T-Lymphocyte Subsets/*immunology ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta1
- Abstract
- Pulmonary fibrosis is a progressive illness characterized by interstitial fibrosis. Although the precise mechanism for pulmonary fibrosis is not completely understood, an immune response involving interferon (IFN)-gamma appears to play a role. Therefore, we examined the functional roles of natural killer T (NKT) cells, which produce IFN-gamma and interleukin-4 on activation, in bleomycin-induced pulmonary fibrosis. In NKT cell-deficient mice, pulmonary fibrosis was worse in terms of histology, hydroxyproline levels, and mortality than in control mice. The transforming growth factor (TGF)-beta1 levels were higher in the lung after injecting bleomycin, and blockade of TGF-beta1 by neutralizing monoclonal antibody attenuated the pulmonary fibrosis in CD1d-/- mice. In contrast, the production of IFN-gamma was reduced in lungs from CD1d-/- mice. Moreover, the adoptive transfer of NKT cells into CD1d-/- mice increased IFN-gamma and reduced TGF-beta1 production, attenuating pulmonary fibrosis. An in vitro assay demonstrated that IFN-gamma was involved in suppressing TGF-beta1 production in cells collected from bronchoalveolar lavage. The adoptive transfer of NKT cells from IFN-gamma-/- mice did not reverse pulmonary fibrosis or TGF-beta1 production in lungs of CD1d-/- mice whereas NKT cells from B6 control mice attenuated fibrosis and reduced TGF-beta1 production. In conclusion, IFN-gamma-producing NKT cells play a novel anti-fibrotic role in pulmonary fibrosis by regulating TGF-beta1 production.
- ISSN
- 0002-9440 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16251408
https://hdl.handle.net/10371/10001
- Files in This Item:
- There are no files associated with this item.
- Appears in Collections:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.