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Role of interferon-gamma in the evolution of murine bleomycin lung fibrosis.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2003 Dec; Vol. 285 (6), pp. L1255-62. Date of Electronic Publication: 2003 Jul 11. - Publication Year :
- 2003
-
Abstract
- IFN-gamma production is upregulated in lung cells (LC) of bleomycin-treated C57BL/6 mice. The present study characterizes the time course, cellular source, and regulation of IFN-gamma expression in bleomycin-induced lung injury. IFN-gamma mRNA in LC from bleomycin-treated mice peaked 3 days after intratracheal instillation. IFN-gamma protein levels were increased at 6 days, as was the percentage of LC expressing IFN-gamma. CD4+, CD8+, and natural killer cells each contributed significantly to IFN-gamma production. IL-12 mRNA levels were increased at 1 day in LC of bleomycin-treated mice. Anti-IL-12 and anti-IL-18 antibodies decreased IFN-gamma production by these cells. To define the role of endogenous IFN-gamma in the evolution of bleomycin lung injury, we compared the effect of bleomycin in mice with a targeted knockout mutation of the IFN-gamma gene (IFN-gamma knockout) and wild-type mice. At 14 days after intratracheal bleomycin, total bronchoalveolar lavage cell counts and lung hydroxyproline were decreased in IFN-gamma knockouts compared with wild-type animals. There was no difference in morphometric parameters of fibrosis. Our data show that enhanced IFN-gamma production in the lungs of bleomycin-treated mice is at least partly IL-12 and IL-18 dependent. Absence of IFN-gamma in IFN-gamma knockout mice does not increase pulmonary fibrosis. Endogenous IFN-gamma may play a proinflammatory or profibrotic role in bleomycin-induced lung fibrosis.
- Subjects :
- Animals
Antimetabolites, Antineoplastic
Bleomycin
Bronchoalveolar Lavage Fluid
Flow Cytometry
Gene Expression immunology
Interferon-gamma metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pulmonary Fibrosis chemically induced
RNA, Messenger analysis
Interferon-gamma genetics
Pulmonary Fibrosis immunology
Pulmonary Fibrosis physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1040-0605
- Volume :
- 285
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12857673
- Full Text :
- https://doi.org/10.1152/ajplung.00303.2002