Journal
JOURNAL OF IMMUNOLOGY
Volume 174, Issue 11, Pages 7250-7256Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.11.7250
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- NHLBI NIH HHS [HL067862, HL47328, R01 HL061803, HL061803, HL29594, R01 HL067862] Funding Source: Medline
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Acute lung injury is a side effect of therapy with a high concentration of inspired oxygen in patients. The molecular mechanism underlining this effect is poorly understood. In this study, we report that overexpression of Stat3C, a constitutive active form of STAT3, in respiratory epithelial cells of a doxycycline-controlled double-transgenic mouse system protects lung from inflammation and injury caused by hyperoxia. In this mouse line, > 50% of transgenic mice survived exposure to 95% oxygen at day 7, compared with 0% survival of wild-type mice. Overexpression of STAT3C delays acute capillary leakage and neutrophil infiltration into the alveolar region. This protection is mediated at least partially through inhibition of hyperoxia-induced synthesis and release of matrix metalloproteinase (MMP)-9 and MMP-12 by neutrophils and alveolar resident cells. In some MMP-9(-/-) mice, prolonged survival was observed under hyperoxic condition. The finding supports a concept that activation of the Stat3 pathway plays a role to prevent hyperoxia-induced inflammation and injury in the lung.
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