Stress-Induced Glucocorticoid Release Upregulates XXXX Expression and Enhances Resistance to Endotoxin-Induced Lethality.

@entity16171 @entity32 @entity19 @entity39115 @entity26 @entity2819 @entity619 @entity2339 @entity842 @entity637
OBJECTIVE: Although psychological and/or physiological stress has been well documented to influence immune responses, the precise mechanism for immunomodulation remains to be elucidated. The present work describes the role of the @entity2339 in the mechanism of stress-mediated enhanced-resistance to lethality after lipopolysaccharide (LPS) injection. METHODS/RESULTS: Preconditioning with restraint stress (RS) resulted in enhanced activation of the @entity2339 in response to LPS injection and suppressed LPS-induced release of proinflammatory cytokines and @entity842 metabolites. @entity39115 -deficient @entity19 ( @entity39115 (-/-)) failed to increase plasma levels of glucocorticoids in response to LPS injection, and exhibited high sensitivity to LPS-induced lethality with enhanced release of proinflammatory cytokines as compared with @entity39115 (+/-) @entity19 . Real-time PCR analysis revealed that RS induced upregulation of @entity16171 ( @entity16171 ) in macrophages in the lung and the liver of @entity39115 (+/-), but not of @entity39115 (-/-), @entity19 . In addition, RS increased @entity16171 -dependent uncoupling activity of isolated mitochondria from the liver of @entity39115 (+/-), but not of @entity39115 (-/-), @entity19 . In vitro study revealed that @entity2819 and @entity619 directly increased @entity16171 expression in @entity19 RAW 264.7 macrophages and suppressed the generation of LPS-induced mitochondrial reactive @entity26 species (ROS) and @entity637 production. Knockdown of @entity16171 by small interfering RNA blunted the @entity619 action for suppressing LPS-induced mitochondrial ROS and @entity637 production. CONCLUSION: The present work suggests that RS enhances activation of the @entity2339 to release glucocorticoids and upregulation of @entity16171 in macrophages, thereby increasing the resistance to endotoxin-induced systemic @entity32 and death.    2015 S. Karger AG, Basel.
