Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease

Gironella, M.; Iovanna, J. L.; Sans, M.; Gil, F.; Peñalva, M.; Closa, D.; Miquel, R.; Piqué, J. M.; Panés, J.
September 2005
Gut;Sep2005, Vol. 54 Issue 9, p1244
Academic Journal
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 56IBD 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.


Related Articles

  • IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease. Kobayashi, T; Okamoto, S; Hisamatsu, T; Kamada, N; Chinen, H; Saito, R; Kitazume, M T; Nakazawa, A; Sugita, A; Koganei, K; Isobe, K; Hibi, T // Gut;Dec2008, Vol. 57 Issue 12, p1682 

    Background: A novel T helper (Th) cell lineage, Th17, that exclusively produces the proinflammatory cytokine interleukin 17 )1L17) has been reported to play important roles in various inflammatory diseases. 1L23 is also focused upon for its potential to promote 1h17. Here, the roles of the...

  • Increased Expression of the Chemokine Fractalkine in Crohn's Disease and Association of the Fractalkine Receptor T280M Polymorphism with a Fibrostenosing Disease Phenotype. Brand, Stephan; Hofbauer, Katrin; Dambacher, Julia; Schnitzler, Fabian; Staudinger, Tanja; Pfennig, Simone; Seiderer, Julia; Tillack, Cornelia; Konrad, Astrid; Göke, Burkhard; Ochsenkühn, Thomas; Lohse, Peter // American Journal of Gastroenterology;Jan2006, Vol. 101 Issue 1, p99 

    BACKGROUND: The fractalkine receptor CX3CR1 has been shown to be involved in inflammation and immune response. Recently, two polymorphisms of CX3CR1 (V249I and T280M) were reported. AIMS: Our aim was to analyze fractalkine expression and the role of CX3CR1 polymorphisms in Crohn's disease (CD)....

  • Protein Microarray Analysis of Disease Activity in Pediatric Inflammatory Bowel Disease Demonstrates Elevated Serum PLGF, IL-7, TGF-β1, and IL-12p40 Levels in Crohn's Disease and Ulcerative Colitis Patients in RemissionversusActive Disease. Kader, Howard A.; Tchernev, Velizar T.; Satyaraj, Ebenezer; Lejnine, Serguei; Kotler, Gregory; Kingsmore, Stephen F.; Patel, Dhavalkumar D. // American Journal of Gastroenterology;Feb2005, Vol. 100 Issue 2, p414 

    OBJECTIVES: Cytokines and growth factors play a major role in the dysregulated immune response in inflammatory bowel disease (IBD). We hypothesized that significant differences exist between the serum cytokine and growth factor profiles of pediatric IBD patients with active disease (AD) and...

  • The Pathogenesis of Mucosal Inflammation in Murine Models of Inflammatory Bowel Disease and Crohn Disease. Strober, Warren; Lúdvíksson, Björn R.; Fuss, Ivan J. // Annals of Internal Medicine;05/15/98, Vol. 128 Issue 10, p848 

    Presents information on mucosal inflammation, with reference to the inflammatory bowel disease and Crohn disease. Discussion on the over-production of Th1 cytokines interleukin-12 and interferon-...; Resemblance of models of intestinal inflammation to Crohn disease; Treatment of the Crohn disease.

  • Acute Idiopathic Pancreatitis Complicating Active Crohn's Disease: Favorable Response to Infliximab Treatment. Triantafillidis, John K.; Cheracakis, Petros; Hereti, Irini A.; Argyros, Nikolaos; Karra, Evangelia // American Journal of Gastroenterology;Nov2000, Vol. 95 Issue 11, p3334 

    Reports on the case of a male patient with Crohn's disease involving concurrently the small and large bowel, which developed idiopathic acute pancreatitis during a severe flare-up of his underlying inflammatory bowel disease. Medical history of the patient; Response of the patient to infliximab...

  • Cytokine and Anti-cytokine Therapies for Inflammatory Bowel Disease. Ogata, Haruhiko; Hibi, Toshifumi // Current Pharmaceutical Design;May2003, Vol. 9 Issue 14, p1107 

    Although the pathogenesis of inflammatory bowel disease (IBD) remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of anti-inflammatory...

  • The classics in perspective. Panés, Julián; Ghosh, Subrata // Gut;Sep2007, Vol. 56 Issue 9, p1184 

    The authors reflect on the development of anti-cytokine therapies as biological agents in treating Crohn's disease and inflammatory diseases. Their therapeutic approach to these diseases has expanded. They noted that gastroenterologists face a remarkable wave of new biological therapies for...

  • Fecal HMGB1 Is a Novel Marker of Intestinal Mucosal Inflammation in Pediatric Inflammatory Bowel Disease. Vitali, Roberta; Stronati, Laura; Negroni, Anna; Di Nardo, Giovanni; Pierdomenico, Maria; del Giudice, Emanuela; Rossi, Paolo; Cucchiara, Salvatore // American Journal of Gastroenterology;Nov2011, Vol. 106 Issue 11, p2029 

    OBJECTIVES:High-mobility group box 1 (HMGB1) is a nuclear protein with functions in the regulation of transcription. In inflammatory conditions, HMGB1 is actively secreted from immune cells in the extracellular matrix, where it behaves as a proinflammatory cytokine. The aim of the present study...

  • Prospective study of immunological factors in non-inflammatory bowel disease enterocutaneous fistulas. Rahbour, Goher; Hart, Ailsa L.; Al-Hassi, Hafid O.; Ullah, Mohammad R.; Gabe, Simon M.; Knight, Stella C.; Warusavitarne, Janindra; Vaizey, Carolynne J. // BMC Surgery;2011, Vol. 11 Issue 1, p12 

    Background: Enterocutaneous fistulas (ECF) are debilitating and usually result following complex abdominal surgery. While there is an association with inflammatory bowel disease (IBD), a large number of fistulas occur after surgery not related to IBD. The consequences of ECF include short bowel...


Read the Article


Sign out of this library

Other Topics