RT Journal Article SR Electronic T1 Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1244 OP 1253 DO 10.1136/gut.2004.056309 VO 54 IS 9 A1 M Gironella A1 J L Iovanna A1 M Sans A1 F Gil A1 M Peñalva A1 D Closa A1 R Miquel A1 J M Piqué A1 J Panés YR 2005 UL http://gut.bmj.com/content/54/9/1244.abstract AB Background and aims: Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation. Patients and methods: Serum PAP levels were determined in healthy controls (n = 29), inflammatory controls (n = 14), and IBD patients (n = 171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor κB (NFκB) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo. Results: Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn’s disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-α induced NFκB activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression. Conclusions: PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NFκB activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.