XXXX Agonist Minimizes Injury and Improves the Immune Response Following Traumatic Shock.

@entity548 @entity19 @entity7111 @entity14075 @entity99 @entity130 @entity2383
Survival from @entity130 requires a coordinated and controlled inflammatory and immune response. Mitochondrial and metabolic responses to stress have been shown to play a role in these inflammatory and immune responses. We hypothesized that increases in mitochondrial biogenesis via a @entity14075 agonist would decrease tissue injury and partially ameliorate the immunosuppression seen following @entity130 . C57Bl/6 @entity19 were subjected to a multiple @entity130 model. @entity19 were pretreated with either 100 mg/kg per day of the @entity14075 agonist, Srt1720, via oral gavage for 2 days prior to @entity130 and extended until the day the animals were killed, or they were pretreated with peroxisome proliferator-activated receptor y coactivator 1a ( @entity7111 ) siRNA via hydrodynamic tail vein injection 48 h prior to @entity130 . Markers for mitochondrial function and biogenesis were measured in addition to splenocyte proliferative capacity and bacterial clearance. Srt1720 was noted to improve mitochondrial biogenesis, mitochondrial function, and complex IV activity following @entity130 (P < 0.05), whereas knockdown of @entity7111 resulted in exacerbation of @entity2383 (P < 0.05). These changes in mitochondrial function were associated with altered severity of @entity99 with significant reductions in serum alanine aminotransferase levels seen in @entity19 treated with srt1720. Splenocyte proliferative capacity and intraperitoneal bacterial clearance were evaluated as markers for overall immune function following @entity548 . Treatment with Srt1720 minimized the @entity130 -induced decreases in splenocyte proliferation (P < 0.05), whereas treatment with @entity7111 siRNA led to diminished bacterial clearance. The @entity7111 signaling pathway is an important regulator of mitochondrial function and biogenesis, which can potentially be harnessed to protect against @entity99 and minimize the immunosuppression that is seen following @entity548 .
