engleski

The impact of CD26 deficiency on peptide YY and substance P expression patterns in Crohn’s disease

Crohn’s disease (CD) is a multifactorial condition characterized by the destructive immune response that failed to be attenuated by common regulatory mechanisms which reduce inflammation and promote intestinal healing1. Present research on CD confirmed the impact of proteases on inflammation onset and the course of the disease, especially the role of dipeptidyl peptidase 4 (DP4). This multifunctional glycoprotein, also known as the CD26 molecule, is expressed on epithelial and immune cells of the gut. The involvement of CD26 in the pathogenesis of CD is effected through proteolytic cleavage of various types of immunomodulatory substrates and its costimulatory function2. Particularly, DP4 directly controls activation/inactivation or changes receptor specificity of numerous cell signaling mediators, including peptide YY (PYY) and substance P (SP). The neuropeptide-receptor interaction represents one of the triggers in some of the key pathways which are dysregulated in CD, so we aimed to investigate the impact of CD26 deficiency on the expression of SP and PYY in experimental CD in CD26 deficient mice. By qPCR and immunodetection, we assessed changes of CD26, SP, and PYY in inflammation, healing, and recovery as well as quantified DP4 activity. We found that CD26 deficiency caused an increase in PYY mRNA expression in inflammation paired with a decrease in its colon concentration, while at the same time SP mRNA, as well as its protein expression, were decreased. DP4 activity in the colon and serum was decreased in the peak of inflammation. It can be concluded that experimental CD affects the expression patterns of both PYY and SP which implicates its involvement in the neuroimmune response in CD pathogenesis.

CD26 deficiency ; Crohn's disease ; peptide YY ; substance P

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