RT Journal Article
SR Electronic
T1 Peroxiredoxin 6 attenuates lipopolysaccharide-induced plasminogen activatro inhibitor 1 expression by regulating autophagy
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3782
VO 40
IS Suppl 56
A1 Yang, Dong
A1 Song, Yuanlin
A1 Sun, Jiayuan
A1 Lin, Tong
A1 Bi, Jing
A1 Bai, Chunxue
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P3782.abstract
AB Objective: To evaluate the roles of Peroxiredoxin(Prdx)6 in the expression of plasminogen activator inhibitor(PAI)-1 in lipopolysaccharide(LPS) induced acute lung injury(ALI). Methods and Results: ALI was induced in Prdx6(-/-) and C57BL/6J mice 4hrs or 24hrs after intratracheal instillation of LPS(5mg/kg), characterized by inflammation in morphology, higher wet/dry ratio, elevated protein concentration and increased neutrophils in bronchial alveolar lavage fluid(BALF), which were more significantly in Prdx6(-/-) mice. After LPS administration, PAI-1 mRNAexpressions were markedly increased in a time-dependant manner and the PAI-1 concentration in BALF were markedly increased at 4hrs and decreased nearly to baseline at 24hrs in Prdx6(-/-) mice compared to C57BL/6J mice. Autophagy was significantly enhenced with higher expression of LC3B in Prdx6(-/-) mice compared to C57BL/6J mice. Primary cultured macrophages were stimulated by LPS (10ug/ml) for 4hrs. The level of reactive oxygen species(ROS) in macrophages from Prdx6 (-/-) mice was significantly higher than that from C57BL/6J mice. The release of PAI-1 was significantly increased in macrophages from Prdx6(-/-) mice compared to wildtype mice after LPS instillation. PAI-1 release was partially suppressed by extracellular signal–regulated kinase(ERK) and p38 mitogen-activated protein kinase inhibitor(MAPK) but not by c-Jun N-terminal kinase inhibitors. Conclusions: In LPS-induced ALI, Prdx6(-/-) mice increased PAI-1 expressions of partially dependent on enhanced autophagy in lungs and p38 MAPK and ERK in macrophages. Thus, Prdx6 possesses anti-fibrinolytic activity under inflammation by regulating autophagy.