Dipeptidyl peptidase-4 expression is reduced in Crohn's disease

Area of Science:

• Gastroenterology
• Enzymology
• Immunology

Background:

• Dipeptidyl peptidase 4 (DP4) is a serine protease that inactivates glucagon-like peptide-2 (GLP-2), a peptide crucial for gut repair.
• DP4 also influences appetite and motility regulators GLP-1 and PYY.
• No prior data existed on DP4 expression in inflammatory bowel disease (IBD).

Purpose of the Study:

• To investigate DP4 expression in tissue and plasma of patients with active Crohn's disease (CD).
• To explore the relationship between DP4 levels and inflammatory activity in CD.
• To examine DP4 regulation in an in vitro model of intestinal inflammation.

Main Methods:

• DP4 protein and mRNA levels were quantified in CD and control tissues and plasma using Western blotting, ELISA, and qPCR.
• Caco-2 intestinal cells were treated with TNFα to model inflammation and assess DP4 expression changes.

Main Results:

• DP4 protein was significantly decreased (~2.7-fold) in active CD tissues compared to controls.
• Plasma DP4 levels were also significantly lower in CD patients, correlating negatively with C-reactive protein levels.
• In vitro, TNFα strongly upregulated DP4 expression in Caco-2 cells, indicating inflammation does not simply downregulate DP4.

Conclusions:

• DP4 is downregulated in both tissue and plasma in active Crohn's disease.
• The observed downregulation is complex and not a direct result of inflammation, as TNFα upregulates DP4.
• Reduced DP4 activity may enhance GLP-2 signaling, supporting gut repair, and suggesting DP4 inhibition as a potential therapeutic strategy for IBD.