Neuronal COX-2 expression in human myenteric plexus in active inflammatorybowel disease

Background-Inflammatory bowel disease (IBD) is associated with changes in c olonic motility which may contribute to the pain and diarrhoea associated w ith exacerbations of this disease. These changes may be mediated by prostag landins which are increased in this condition. Increased expression of the inducible isoform of cyclo-oxygenase (COX-2) has been found in active IBD a lthough its cellular distribution remains uncertain. Aims-To evaluate the cellular distribution of COX-2 in active IBD. Patients and methods-Using reverse transcription-polymerase chain reaction, in situ hybridisation, and immunohistochemistry, COX-2 expression was eval uated in 12 colectomy specimens from patients with active ulcerative coliti s (UC), and six specimens from patients with Crohn's colitis that had faile d medical therapy. Histologically normal colon was obtained from 12 patient s having resection for colorectal neoplasia and evaluated as above, acting as control specimens. Results-All specimens expressed COX-2 mRNA, with some 6-8-fold increase in inflamed tissues on densitometric analysis (both UC and Crohn's) compared w ith controls. In situ hybridisation localised this mRNA to myenteric neural cells, surrounding smooth muscle cells, and inflammatory cells of the lami na propria in the IBD specimens, with some weaker labelling seen in the epi thelium. No COX-2 labelling was seen in normal tissues. Immunohistochemistr y confirmed these sites of COX-2 expression in all inflamed specimens, with absence of immunoreactivity in control tissues. Conclusions-These findings provide the first evidence of COX-2 expression i n neural cells of the myenteric plexus in active IBD which, via increased p rostaglandin synthesis at this site, may contribute to the dysmotilty seen in this condition.