Expression of peroxisome proliferator activated receptor gamma coactivator 1 (PGC‐1) on the immune response to bacteria

Introduction/Objective Inflammatory response during sepsis requires energy expenditure from immune cells. Since the transcription coactivator PGC‐1 controls cell energy homeostasis, we aimed to determine whether PGC‐1 may modulate the immune response in an experimental model of sepsis. Methods Live bacteria were injected intraperitoneally in Balb/C mice and PGC‐1β expression was evaluated by quantitative PCR in peritoneal macrophages. Further, mice (20 animals in each group) were submitted to cecal ligation and puncture (CLP). Group 1 received intraperitoneal injections of antisense oligonucleotide (ASO) against PGC‐1β (3,0 nmol) three days before and three days after CLP. Group 2 was given no specific treatment. The animals were followed for 72 hours and mortality was evaluated every 12 hours. Results Increased PGC‐1β expression was observed in macrophages from animals exposed to bacteria compared to controls (2.7±0.5 vs. 1.0±0.2, respectively, p<0.05). We further evaluated whether PGC‐1β absence would interfere with the response to acute bacterial aggression in vivo. Mice from Group 1, where PGC‐1β expression was blocked, showed an 80% mortality after 72 hours, while animals from Group 2 had a mortality rate of 63% (p=0,7714). Conclusions PGC‐1β is up‐regulated during bacterial infection, however, abolishing PGC‐1β expression did not affect mortality of septic mice. Financial support: FAPESP