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Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease.
Gut 2005; 54(9):1244-53Gut

Abstract

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 kappaB (NFkappaB) 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-alpha induced NFkappaB 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 NFkappaB 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.

Authors+Show Affiliations

Gastroenterology Department, Institut de Malalties Digestives, Hospital Clínic, Villarroel 170 08036 Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15870231

Citation

Gironella, M, et al. "Anti-inflammatory Effects of Pancreatitis Associated Protein in Inflammatory Bowel Disease." Gut, vol. 54, no. 9, 2005, pp. 1244-53.
Gironella M, Iovanna JL, Sans M, et al. Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease. Gut. 2005;54(9):1244-53.
Gironella, M., Iovanna, J. L., Sans, M., Gil, F., Peñalva, M., Closa, D., ... Panés, J. (2005). Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease. Gut, 54(9), pp. 1244-53.
Gironella M, et al. Anti-inflammatory Effects of Pancreatitis Associated Protein in Inflammatory Bowel Disease. Gut. 2005;54(9):1244-53. PubMed PMID: 15870231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease. AU - Gironella,M, AU - Iovanna,J L, AU - Sans,M, AU - Gil,F, AU - Peñalva,M, AU - Closa,D, AU - Miquel,R, AU - Piqué,J M, AU - Panés,J, Y1 - 2005/05/03/ PY - 2005/5/5/pubmed PY - 2005/12/13/medline PY - 2005/5/5/entrez SP - 1244 EP - 53 JF - Gut JO - Gut VL - 54 IS - 9 N2 - 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 kappaB (NFkappaB) 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-alpha induced NFkappaB 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 NFkappaB 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. SN - 0017-5749 UR - https://www.unboundmedicine.com/medline/citation/15870231/Anti_inflammatory_effects_of_pancreatitis_associated_protein_in_inflammatory_bowel_disease_ L2 - http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=15870231 DB - PRIME DP - Unbound Medicine ER -