Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis

Abstract

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients’ demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC.

Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses

“…However, even if these facts were true in the case of MPS, due to an unknown role of GAL in degeneration/protection of neurons, the use of GAL as a The neprilysin protein (the MME gene product) is known primarily for its increased expression in one of the pre-B phenotype of acute lymphocytic leukemia, thanks to which it owes its second name, common acute lymphoblastic leukemia antigen (CALLA) [107]. There are also reports indicating cases of a decrease in its level in ulcerative enteritis [108] or heart failure [109], and mutations occurring in some diseases, such as autosomal-recessive Charcot-Marie-Tooth disease type 2, characterized by deformation of the feet and the disappearance of some muscles and reflexes [110], and inherited peripheral neuropathies [111]. Furthermore, elevated levels of some neprilysin substrates (glucagon and insulin) have been described as the main cause of diabetes [112], and one of the symptoms associated with sickle cell disease (substance P) [113].…”

Effect of Qinbai Qingfei Concentrated Pellets on substance P and neutral endopeptidase of rats with post-infectious cough

“…More importantly, it is commonly believed that neurogenic inflammation has been involved in the pathogenesis of PIC [ 11 ]. NEP, also known as CD10, which is the primary degrading enzyme of neuropeptides in airway that hydrolyzes neuropeptides such as SP and CGRP [ 30 ]. Excessive neuropeptides expression and impaired NEP activity in the lung have been testified in respiratory viral infection and pulmonary diseases [ 31 ].…”

Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells

“…In UC, substance P and VIP decreased simultaneously. Further study is needed to determine the role of the neuropeptide in UC[ 43 ].…”