Source: Annual Congress 2010 - Acute respiratory failure

Abstract

Background: mTOR pathway, a key cellular signaling pathway associated with cellular functions, has distinct roles in inflammatory process. In this study, selective mTOR inhibitor rapamycin (RAPA) was used to test whether mTOR activation is critical in a murine model of LPS-induced acute lung injury.
Methods: Mice pretreated with or without RAPA (8mg/kg body weight for consecutive five days) received LPS by intratracheal administration.
Results: The phosphorylation of S6, a major downstream target of mTOR, increased significantly in murine lung tissue after LPS stimulation, which was blocked by RAPA. Administration of RAPA diminished the levels of TNF-α (LPS vs LPS+Rapa: 1672.74±193.73 vs 539.17±140.47, pg/ml, P<0.01) and IL-6 (LPS vs LPS+RAPA: 7790.88±1170.54 vs 1968.57 ±474.62, pg/ml, P<0.01) in BAL fluid, and abrogated IL-1βup-regulation (LPS vs LPS+RAPA: 6394.20 ±904.59 vs 3196.08±487.46, pg/mg protein, P <0.01) but reinforced MMP-9 up-regulation (LPS vs LPS+RAPA: 17.98±3.17 vs 37.86±19.00, pg/mg protein, P <0.05) induced by LPS in lung tissue. However, RAPA had little effects to the severity of ALI , as determined by wet-dry weight ratio, neutrophils cell in BAL fluid, and histopathology changes of ALI as well as the thickness of alveolar septum. Also, there was no difference in lethality of LPS-mediated ALI between the rapamycin and vehicle pretreated mice (P>0.05, Kaplan-Meier test).
Conclusion: mTOR is activated in the LPS-induced ALI. However, inhibition of mTOR has a limited effect in the overall severity and survival.
Grant support: 973 Program of China (2009CB522106).

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Citations should be made in the following way:
J. Gao, K. F. Xu, L. Wang, Y. Gui, X. Tian (Beijing, China). Activation of mammalian target of rapamycin (mTOR) in a murine model of lipopolysaccharide (LPS) -induced acute lung injury. Eur Respir J 2010; 36: Suppl. 54, 2282

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