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Natural killer T (NKT) cells attenuate bleomycin-induced pulmonary fibrosis by producing interferon-gamma

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Authors

Kim, J. H.; Kim, H. Y.; Kim, S.; Chung, J. H.; Park, W. S.; Chung, D. H.

Issue Date
2005-10-28
Publisher
American Society for Investigative Pathology (ASIP)
Citation
Am J Pathol. 2005 Nov;167(5):1231-41.
Keywords
Adoptive TransferAnimalsBleomycinBody WeightCells, CulturedDisease Models, AnimalHydroxyproline/analysisInterferon-gamma/*biosynthesis/geneticsKiller Cells, Natural/*immunologyLung/drug effects/*pathologyMaleMiceMice, Inbred C57BLMice, KnockoutPulmonary Fibrosis/chemically induced/*immunology/*pathologyT-Lymphocyte Subsets/*immunologyTransforming Growth Factor beta/metabolismTransforming 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/10371/22624
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