Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis

Tsung-Chieh Shih; Sen-Yung Hsieh; Yi-Yueh Hsieh; Tse-Chin Chen; Chien-Yu Yeh; Chun-Jung Lin; Deng-Yn Lin; Cheng-Tang Chiu; Ando, Takafumi
March 2008
World Journal of Gastroenterology;3/21/2008, Vol. 14 Issue 11, p1759
Academic Journal
AIM: To investigate the role of nuclear factor of activated T cell 2 (NFAT2), the major NFAT protein in peripheral T cells, in sustained T cell activation and intractable inflammation in human ulcerative colitis (UC). METHODS: We used two-dimensional gel-electrophoresis, immunohistochemistry, double immunohistochemical staining, and confocal microscopy to inspect the expression of NFAT2 in 107, 15, 48 and 5 cases of UC, Crohn's disease (CD), non-specific colitis, and 5 healthy individuals, respectively. RESULTS: Up-regulation with profound nucleo-translocation/ activation of NFAT2 of lamina propria mononuclear cells (LPMC) of colonic mucosa was found specifi cally in the affected colonic mucosa from patients with UC, as compared to CD or NC ( P < 0.001, Kruskal-Wallis test). Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T, but was less prominent in CD4+ T cells or CD20+B cells. It was strongly associated with the disease activity, including endoscopic stage (Ï„ = 0.2145, P = 0.0281) and histologic grade (Ï„ = 0.4167, P < 0.001). CONCLUSION: We disclose for the first time the nucleo-translocation/activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis. Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity. Since activation of NFAT2 is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways, our results not only provide new insights into the mechanism for sustained intractable inflammation, but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.


Related Articles

  • The RANKL/OPG system is activated in inflammatory bowel disease and relates to the state of bone loss. Moschen, A. R.; Kaser, A.; Enrich, B.; Ludwiczek, O.; Gabriel, M.; Obrist, P.; Wolf, A. M.; Tilg, H. // Gut;Apr2005, Vol. 54 Issue 4, p479 

    Background and aims: A substantial proportion of patients with inflammatory bowel disease (IBD) develops osteopenia and osteoporosis in the course of disease. Recent data from a mouse model of colitis suggest that the receptor activator of nuclear factor kappa B (RANKL)/osteoprotegerin (OPG)...

  • Effects of recombinant human intestinal trefoil factor on trinitrobenzene sulphonic acid induced colitis in rats. Li, Jin; Zhou, Rui; He, Wen-cheng; Xia, Bing // Molecular Biology Reports;Oct2011, Vol. 38 Issue 7, p4787 

    Intestinal trefoil factor (ITF) has been proved to be effective in treatment of ulcerative colitis. However, the mechanisms of it remain unclear. In this study, we observed the effects of combined treatment with 5-aminosalicylic acid (5-ASA) and recombinant human ITF (rhITF) on the expression of...

  • Activation of NF-κB in intestinal epithelial cells by E. coli strains isolated from the colonic mucosa of IBD patients. La Ferla, Katia; Seegert, Dirk; Schreiber, Stefan // International Journal of Colorectal Disease;Jul2004, Vol. 19 Issue 4, p334 

    Background and aims. The involvement of bacteria in the pathogenesis of inflammatory bowel disease has been discussed for several years. In this study we evaluated the ability of E. coli isolates from inflamed and noninflamed colonic mucosa to activate NF-κB. Materials and methods. Fifteen...

  • Inflammatory disease: Local therapy for inflammatory bowel disease. Brazil, Melanie // Nature Reviews Drug Discovery;Dec2005, Vol. 4 Issue 12, p958 

    The article reports on the successful treatment of both murine models of ulcerative colitis and Crohn's disease with locally or systematically delivered nuclear factor-;A. The authors showed that intrarectal or intraperitoneal administration of decoy oligodeoxynucleotides, which were...

  • Evidence for a Potential Role of Metallothioneins in Inflammatory Bowel Diseases. Waeytens, Anouk; De Vos, Martine; Laukens, Debby // Mediators of Inflammation;2009, Vol. 2009, Special section p1 

    Inflammatory bowel diseases (IBDs) are a group of chronic, relapsing, immune-mediated disorders of the intestine, including Crohn's disease and ulcerative colitis. Recent studies underscore the importance of the damaged epithelial barrier and the dysregulated innate immune system in their...

  • Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. Visekruna, Alexander; Joeris, Thorsten; Seidel, Daniel; Kroesen, Anjo; Loddenkemper, Christoph; Zeitz, Martin; Kaufmann, Stefan H. E.; Schmidt-Ullrich, Ruth; Steinhoff, Ulrich // Journal of Clinical Investigation;Dec2006, Vol. 116 Issue 12, p3195 

    Enhanced NF-kappaB activity is involved in the pathology of both forms of inflammatory bowel disease (IBD), Crohn disease (CD) and ulcerative colitis (UC). Here we analyzed the mechanism of proteasome-mediated NF-kappaB activation in CD and UC. Our studies demonstrate that the subunit...

  • Regulation of nuclear factor-κΒ in intestinal epithelial cells in a cell model of inflammation. Homaidan, Fadia R.; Chakroun, Iman; El-Sabban, Marwan E. // Mediators of Inflammation;Oct2003, Vol. 12 Issue 5, p277 

    Studies the role of nuclear factor (NF)-kappa beta, a pro-inflammatory and anti-apoptotic factor, in IL-1-treated intestinal epithelial cells. Assessment of NF-kappa beta activity and levels of apoptotic proteins by electrophoretic mobility; Ratio of mRNA levels of anti-apoptotic to apoptotic...

  • Melatonin reduces TNF-a induced expression of MAdCAM-1 via inhibition of NF-kB. Sasaki, Makoto; Jordan, Paul; Joh, Takashi; Itoh, Makotoh; Jenkins, Michael; Pavlick, Kevin; Minagar, Alireza; Alexander, Steven J. // BMC Gastroenterology;2002, Vol. 2, p9 

    Background: Endothelial MAdCAM-1 (mucosal addressin cell adhesion molecule-1) expression is associated with the oxidant-dependent induction and progress of inflammatory bowel disease (IBD). Melatonin, a relatively safe, potent antioxidant, has shown efficacy in several chronic injury models may...

  • The role of protein kinase CK2 in intestinal epithelial cell inflammatory signaling. Parhar, Kuljit; Morse, Jennifer; Salh, Baljinder // International Journal of Colorectal Disease;Jun2007, Vol. 22 Issue 6, p601 

    The transcription factor NF-κB is believed to play a key pathophysiological role in chronic intestinal inflammation. Further characterization of its mechanism of regulation, predominantly through cell signaling pathways, may provide clues as to the means of its intervention. One such...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics