Effect of NF-κB and p38 MAPK in activated monocytes/macrophages on pro-inflammatory cytokines of rats with acute pancreatitis

Abstract

AIM: Proinflammatory cytokines TNF-α and IL-6 play a main role in acute pancreatitis (AP). Cytokine biosynthesis runs through two major signaling pathways at the level of proteins: nuclear transcription factor-κB (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK). The aim of the study was to investigate the effect of NF-κB and p38 MAPK in activated monocytes/macrophages on cytokines of rats with acute pancreastitis. METHODS:Taurocholate (3 % and 5 %) at doses of 1 mL/kg was administered into the biliopancreatic duct of male Sprague-Dawley (SD) rats to reduce acute edematous pancreariris (AEP) and acute necrotizing pancreatitis (ANP). Pancreatic tissues were prepared immediately after death. At this point, blood was obtained for determination of serum amylase and pro-inflammatory TNF-α and IL-6. Activated monocytes/macrophages were captured from blood and so were ascites. NF-κB and p38 MAPK in activated monocytes/ macrophages were measured by immunohistochemistry method. Pancreatic tissue samples were prepared for routine light microscopy, using hematoxylin and eosin (HE) staining. RESULTS:The serum levels of amylase were 3 056.00± 1 232.35 IU/L and 4 865.12±890.34 IU/L at 3 and 6 hours in ANP group, which were significantly higher than those (3 056.00±1 232.35 IU/L and 3 187.17±821.16 IU/L) (P<0.05, respectively) in AEP group. In ascites the levels were 3.32±1.01 g and 3.76±1.12 g at 3 and 6 hours in ANP group, which were significantly higher than those (1.43±1.02 g and 2.56±1.21 g) (P<0.05, respectively) in AEP group. The serum levels of TNF-α were 54.27±23.48 pg/ml and 67.83±22.02 pg/ml in AEP group and 64.28±20.79 pg/ml and 106.59± 43.71 pg/ml in ANP group, and the serum levels of IL-6 were 428.12±140.30 pg/ml and 420.13±139.40 pg/ml in AEP group and 1 600.32±309.78 pg/ml and 2 203.76±640.85 pg/ml in ANP group, which were far significantly higher than those in sham group (P<0.001, respectively). The serum level of TNF-α 6 hours after establishment of the studied model and that of IL-6 at 3 and 6 hours in ANP group were significantly higher than those in AEP (P<0. 05, P<0.001, P<0.05). In ANP group, the levels of serum TNF-α and IL-6 6 hours after establishment of the studied model were significantly higher than those 3 hours after establishment of studied model (P<0.05, P<0.05, respectively). Three and 6 hours after establishment of the model, typical pathological changes of AEP and ANP were found,

Taurine Attenuates Liver Injury by Downregulating Phosphorylated p38 MAPK of Kupffer Cells in Rats with Severe Acute Pancreatitis

“…Also in hepatocyte and acinar cells, the increase of p38 MAPK phosphorylation could be induced by pancreatitis-associated ascitic fluid [31,32]. In addition, the expression of p38 MAPK in activated monocytes/macrophages was upregulated after introduction of the SAP model [33]. Inhibiting expression of p38 MAPK ameliorates severity of the disease [8].…”

Effect of resveratrol on peritoneal macrophages in rats with severe acute pancreatitis

“…SIRS might result in multiple organ failure [6][7][8][9], in which lung dysfunction is the major cause of death in patients with SAP. Macrophages are the main infl ammatory cells that modulate the progression of SAP [10][11][12][13][14][15][16]. The activation of macrophages can lead to the release of a number of infl ammatory mediators, including TNF-a, IL-1, interleukin-6 (IL-6), interleukin-8 (IL-8), platelet-activating factor (PAF) and NO.…”

Pancreatitis-Associated Ascitic Fluid Induces Proinflammatory Cytokine Expression in THP-1 Cells by Inhibiting Anti-inflammatory Signaling

“…Studies show that p38 was activated in the pancreatic tissue and circulating monocytes in experimental AP. 19,25 We conclude that PAAF can induce the activity of p38, which may play an important role in PAAF inducing the expression of TNF-> and IL-6.…”