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

引用

World Journal of Gastroenterology 2008年第11期14卷 1759-1767页

作者： tsung-Chieh Shih Sen-Yung Hsieh Yi-Yueh Hsieh tse-Chin Chen Chien-Yu Yeh Chun-Jung Lin Deng-Yn Lin Cheng-tang Chiu Clinical Proteomics Center Chang Gung Memorial HospitalTaoyuan 333Taiwan Clinical Proteomics Center Chang Gung Memorial HospitalTaoyuan 333Taiwan Department of Hepato-GastroenterologyChang Gung Memorial HospitalChang Gung University School of Medicine Taoyuan 333Taiwan Department of Anatomic Pathology Chang Gung Memorial HospitalTaoyuan 333Taiwan Department of Colorecto-Surgery Chang Gung Memorial HospitalTaoyuan 333Taiwan Department of Hepato-Gastroenterology Chang Gung Memorial HospitalChang Gung University School of Medicine Taoyuan 333Taiwan

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 specifically in the affected colonic mucosa from patients with UC,as compared to CD or NC(Ptest).Nucleo-translocation/activation of NFAt2 primarily occurred in CD8+t,but was less prominent in CD4+t cells or CD20+B *** was strongly associated with the disease activity,including endoscopic stage (τ=0.2145,P=0.0281)and histologic grade(τ=0.4167, Pthe first time the nucleo-translocation/activatin of NFAt2 in lamina propria mononuclear cells in ulcerative *** of NFAt2 was specific for ulcerative colitis and highly associated with disease *** activation of NFAt2is 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.

关键词： nuclear factor of activated t cells Ulcerative colitis Inflammatory bowel disease nuclear factor of activated t cells cl nuclear factor of activated t cells 2

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