Glucocorticoids aggravate hyperoxia-induced lung injury through decreased nuclear factor-kappa B activity
1 Department of Pediatrics, 2 Department of Pathology, and 3 Division of Endocrinology, Department of Internal Medicine, University of Geneva Medical School, 1211 Geneva 4, Switzerland We previously reported that exposure of mice to hyperoxia is characterized by extensive lung cell necrosis and a...
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Published in | American journal of physiology. Lung cellular and molecular physiology Vol. 284; no. 1; pp. 197 - L204 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Physiological Society
01.01.2003
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Pediatrics,
2 Department of Pathology, and 3 Division
of Endocrinology, Department of Internal Medicine, University of
Geneva Medical School, 1211 Geneva 4, Switzerland
We previously reported that
exposure of mice to hyperoxia is characterized by extensive lung cell
necrosis and apoptosis, mild inflammatory response, and
elevated circulating levels of corticosterone. Administration of
hydroxycortisone acetate during hyperoxia aggravated lung injury. Using
adrenalectomized (ADX) and sham-operated (sham) mice, we studied the
role of the glucocorticoids in hyperoxia-induced lung injury. Lung
damage was attenuated in ADX mice as measured by lung weight and
protein and cell content in bronchoalveolar lavage and as seen by light
microscopy. Mortality was delayed by 10 h. Nuclear factor- B
(NF- B) activity was significantly decreased in lungs of sham mice
exposed to hyperoxia but was preserved in ADX mice. There was a
correlation between NF- B activity in ADX mice and decreased levels
of I B . In contrast, activator protein-1 activity increased
similarly in both groups of mice. Levels of interleukin-6 (IL-6), a
transcriptional target of NF- B, were higher in bronchoalveolar
lavage and serum of ADX than sham mice. However, the protective effect
of ADX was not mediated by IL-6, because administration of recombinant
human IL-6 to sham mice did not prevent lung damage. These results
demonstrate that the adrenal response aggravates alveolar injury and is
likely to be mediated by the decrease of NF- B function involved in
cell survival.
mice; oxygen; apoptosis; steroid |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1040-0605 1522-1504 |
DOI: | 10.1152/ajplung.00239.2002 |