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Glucocorticoids aggravate hyperoxia-induced lung injury through decreased nuclear factor-kappa B activity

Published in American journal of physiology. Lung cellular and molecular physiology. 2003, vol. 284, no. 1, p. L197-204
Abstract 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-kappaB (NF-kappaB) activity was significantly decreased in lungs of sham mice exposed to hyperoxia but was preserved in ADX mice. There was a correlation between NF-kappaB activity in ADX mice and decreased levels of IkappaBalpha. In contrast, activator protein-1 activity increased similarly in both groups of mice. Levels of interleukin-6 (IL-6), a transcriptional target of NF-kappaB, 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-kappaB function involved in cell survival.
Keywords AdrenalectomyAnimalsApoptosisCorticosterone/metabolismGlucocorticoids/pharmacologyHyperoxia/metabolism/pathologyI-kappa B Proteins/metabolismInterleukin-6/pharmacologyLung/drug effects/metabolism/pathologyMiceMice, Inbred C57BLNF-kappa B/antagonists & inhibitorsProline/analogs & derivatives/pharmacologyPulmonary AlveoliPulmonary Edema/prevention & controlThiocarbamates/pharmacologyThymus Gland/pathology/physiopathologyTranscription Factor AP-1/metabolism
PMID: 12388343
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Research group Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182)
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BARAZZONE, Constance et al. Glucocorticoids aggravate hyperoxia-induced lung injury through decreased nuclear factor-kappa B activity. In: American journal of physiology. Lung cellular and molecular physiology, 2003, vol. 284, n° 1, p. L197-204. doi: 10.1152/ajplung.00239.2002 https://archive-ouverte.unige.ch/unige:55336

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Deposited on : 2015-04-09

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