Study of Expression Patterns and Levels of Neurotrophins and Neurotrophin Receptors in Ulcerative Colitis

Abstract

Neurotrophins may be involved in ulcerative colitis (UC). Yet, it is unclear whether if their effects should be blocked. In this study, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors were examined by immunohistochemistry, ELISA, and RT-PCR. BDNF immunoreaction was detected in nerve structures in particular, and NGF immunoreaction was detected in lamina propria cells. Cellular NGF immunoreaction was generally observed to be higher in the mucosa of UC patients than in the controls. In addition, UC patients demonstrated significantly higher p75 immunoreaction (P = 0.010) in lamina propria cells. The controls expressed significantly higher BDNF immunoreaction in the nerve structures than did UC patients (P = 0.000). However, the UC group showed marked interindividual variation in expression of neurotrophins and neurotrophin receptors. This included variation at the mRNA level for NGF. Differences with the controls were most pronounced in UC specimens demonstrating great infiltration of inflammatory cells and marked tissue derangement. Corticosteroid treatment seemed to affect neurotrophin production in lamina propria cells but not in nerve structures. These observations demonstrate that up-regulation and down-regulation of neurotrophins occur in different structural components in response to the disease process. Massive inflammation seemed to be correlated with decreased neurotrophin immunoreaction in nerve structures, but there was a tendency toward increased neurotrophin production in lamina propria cells. Our study shows that UC patients are not a uniform group in their expression of neurotrophins, a fact that should be considered when discussing therapeutic interventions.