Trypsin may be associated with duodenal eosinophils through the expression of PAR2 in early chronic pancreatitis and functional dyspepsia with pancreatic enzyme abnormalities

Abstract

Background Early chronic pancreatitis (ECP) has been reported to advance into chronic pancreatitis, it may be critical to differentiate the pathophysiology of ECP and functional dyspepsia (FD) in patients with pancreatic enzyme abnormalities (FD-P). This study aimed to clarify differences in the pathophysiology of ECP and FD-P and to determine whether duodenal inflammatory responses in the two diseases were associated with protease-activated receptor (PAR) 2, as the trypsin receptor. Methods Eighty patients who presented with FD-P and ECP were enrolled. In duodenal specimens, PAR2 mRNA levels were determined using real-time PCR. Using immunostaining, CD68-, GLP-1-, PRG2-, and CCR2-positive cells, tight junction proteins, and PAR 2 were evaluated. Results There were no significant differences in clinical symptoms and gastric motility between ECP and FD-P patients. The CD68-positive cells infiltrations and occludin expression levels in the duodenal mucosa of patients with FD-P were significantly (p<0.001 and p = 0.048, respectively) lower than those in patients with ECP. Although serum trypsin levels in ECP and FD-P patents were significantly (p<0.05 and p<0.001, respectively) associated with duodenal eosinophils counts, elevated trypsin levels were not significantly associated with degranulated eosinophils, occludin, claudin-1 and ZO-1 expression levels in the duodenum of either group. PAR2 mRNA levels were increased in the duodenum of patients with ECP and FD-P. PAR2 was localized in the epithelial cells of the duodenal mucosa and the surface of degranulated eosinophils in ECP and FD-P patients. Conclusions Elevated trypsin levels might be partly associated with duodenal inflammatory responses through PAR2-related degranulated eosinophils and the reduction of occludin in patients with ECP and FD-P.

Comparison of pancreatic enzyme abnormalities and protease‐activated receptor‐2‐positive eosinophils in the duodenum of patients with functional dyspepsia‐irritable bowel syndrome overlap with functional dyspepsia alone in Asian populations

“…Because PAR2 is ubiquitously expressed in gastrointestinal mucosal cells, smooth muscle cells, and neurons, activation of PAR2 induces a wide range of processes such as triggering intestinal secretion, modulating gastrointestinal motility, 40,41 participating in colonic inflammatory reactions and visceral hypersensitivity 42 . We have previously reported that PAR2 expression was localized in the duodenal epithelium and duodenal eosinophils in patients with FD with pancreatic enzyme abnormalities (FD‐P) 21 . We have also reported that PAR2 was localized in degranulated eosinophils in the duodenum of patients with FD‐P 21 .…”

Apolipoprotein A2 isoforms associated with exocrine pancreatic insufficiency in early chronic pancreatitis

“…The clinical symptoms of patients with FD were estimated based on the Rome IV criteria. 19,20 At least one of the following clinical symptoms must be present in patients with FD: early satiation, bothersome postprandial fullness, epigastric pain, or epigastric burning. Postprandial distress syndrome and epigastric pain syndrome were diagnosed when symptoms persisted for at least 3 months, and the onset of symptoms was at least 6 months before the diagnosis.…”

“…In this study, FD symptoms, including epigastric pain, epigastric burning, postprandial fullness, and early satiety, as well as treatment satisfaction were assessed based on the Rome IV classification as follows: 0, none; 1, very mild; 2, mild; 3, moderate; 4, severe; and 5, very severe. 19,20 Clinical symptoms were also evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). 21 In particular, we used the mean GSRS score and its 15 GI symptoms for the evaluation of dyspeptic symptoms.…”

“…The clinical symptoms of patients with FD were estimated based on the Rome IV criteria 19,20 . At least one of the following clinical symptoms must be present in patients with FD: early satiation, bothersome postprandial fullness, epigastric pain, or epigastric burning.…”

“…Postprandial distress syndrome and epigastric pain syndrome were diagnosed when symptoms persisted for at least 3 months, and the onset of symptoms was at least 6 months before the diagnosis. In this study, FD symptoms, including epigastric pain, epigastric burning, postprandial fullness, and early satiety, as well as treatment satisfaction were assessed based on the Rome IV classification as follows: 0, none; 1, very mild; 2, mild; 3, moderate; 4, severe; and 5, very severe 19,20 . Clinical symptoms were also evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) 21 .…”