Nerve growth factor and Trk high affinity receptor (TrkA) gene expression in inflammatory bowel disease

Background-Nerve growth factor (NGF), a target derived factor for survival and maintenance of peripheral and central neurones, has been implicated in several chronic inflammatory processes. Aims-To analyse the concomitant presence of NGF and its high affinity recep tor TrkA in patients undergoing surgery for Crohn's disease (CD) and ulcera tive colitis (UC). Patients-CD tissues were obtained from 33 patients and U C tissue samples from 12 patients undergoing surgery. Normal intestinal tis sue samples were obtained from 30 individuals through an organ donor progra mme. Methods-Expression of NGF and TrkA. was studied by northern blot analysis. Using in situ hybridisation and immunohistochemistry, the respective mRNA m oieties and proteins were localised. Western blot analysis was used to conf irm the specificity of NGF and TrkA antibodies. Results-In CD, NGF mRNA was increased in 60% (2.4-fold; p<0.01) and TrkA rn RNA in 54% (1.3-fold; p<0.05) of samples. In UC, NGF mRNA expression was en hanced in 58% (2.4-fold; p<0.01) and TrkA mRNA expression in 50% (1.5-fold; p<0.05) of samples. In situ hybridisation showed that NGF and TrkA mRNA we re often concomitantly present in polymorphonuclear-like cells of the lamin a propria, in mast cells, and in a few ganglia of Auerbach's plexus and Mei ssner's plexus. Immunohistochemistry revealed that lamina propria cells and inflammatory cells (mainly mast cells) were NGF and TrkA immunopositive. N GF was also present in Meissner's plexus (especially in CD) and TrkA in ent eric glia surrounding intestinal ganglia. Conclusions-The concomitant enhanced expression of NGF and its receptor sug gests activation of this pathway in chronic inflammation in CD and UC. The presence of NGF and TrkA in both neural and non-neural structures in CD and UC supports the hypothesis that neuroimmune interactions occur and are act ivated in both disorders.