PGC-1α Expression Is Increased in Leukocytes in Experimental Acute Pancreatitis

Abstract

Severe acute pancreatitis (AP) induces a systemic inflammatory disease that is responsible for high mortality rates, particularly when it is complicated by infection. Therefore, differentiating sepsis from the systemic inflammation caused by AP is a serious clinical challenge. Considering the high metabolic rates of leukocytes in response to stress induced by infection, we hypothesized that the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1α), a master regulator of mitochondrial biogenesis and function, would be distinctly expressed during inflammation or infection and, therefore, could constitute a useful marker to differentiate between these two conditions. Rats were subjected to injection of taurocholate into the main pancreatic duct, which caused a severe AP with high amylase levels and white blood cell counts. In these animals, a marked increase in PGC-1α mRNA levels in circulating leukocytes was observed 48 h after the surgical procedure, a time when bacteremia is present. Antibiotic treatment abolished PGC-1α up-regulation. Moreover, PGC-1α expression was higher in peritoneal macrophages from animals subjected to a bacterial insult (cecal ligation and puncture) than in animals with AP. In isolated macrophages, we also observed that PGC-1α expression is more prominent in the presence of a phagocytic stimulus (zymosan) when compared to lipopolysaccharide-induced aseptic inflammation. Moreover, abolishing PGC-1α expression with antisense oligos impaired zymosan phagocytosis. Together, these findings suggest that PGC-1α is differentially expressed during aseptic inflammation and infection and that it is necessary for adequate phagocytosis. These results could be useful in developing new tests for differentiating infection from inflammation for clinical purposes in patients with AP.

Effects of diazoxide in experimental acute necrotizing pancreatitis

“…Sodium taurocholate caused severe histologic damage similar to that observed for other experimental models 14 – 16 . Significant edema, intense infiltration of leukocytes and intra-pancreatic bleeding shows the similarity of the histopathology of experimental lesions with moderate-to-severe pancreatitis in humans 14 , 15 . Mortality in the control group at 24 h was 22%, similar to the mortality (20%) obtained using glycodeoxycholic acid (5–10 mmol) by other research teams.…”

Exercise Cuts Both Ways with ROS in Remodifying Innate and Adaptive Responses: Rewiring the Redox Mechanism of the Immune System during Exercise

“…In addition, exercise-induced ROS-dependent pathways such as PGC-1alpha are linked with increased mitochondrial biogenesis, antioxidant expression, and inhibition of inflammatory pathways in macrophages [ 73 , 74 , 75 ]. Llimona et al showed that PGC-1alpha expression is crucial for phagocytic stimulus in acute pancreatitis [ 76 ].…”

Bacterial community mapping of the intestinal tract in acute pancreatitis rats based on 16S rDNA gene sequence analysis

“…[2][3][4][5][6] Acute pancreatitis (AP) is an inammatory disorder of the pancreas encountered in emergency settings with an annual incidence range of 13-45/100 000 inhabitants. [7][8][9] Approximately 20% of AP patients develop necrotizing pancreatitis with a high mortality risk, mostly attributed to sepsis and infection of pancreatic and peripancreatic necrotic tissue induced by gutderived bacteria overgrowth and subsequent bacterial translocation. 10 Recently, it has been established that disruption of gut microora is signicantly correlated with "second hit summit" involved in the progression of AP, which demonstrated that gut microbiota is a promising modulator of inammatory cascade in AP pathophysiology.…”