Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis

Melgar, Silvia; Yeung, M M; Bas, Anna; Forsberg, Göte; Suhr, Ole B.; Öberg, Åke; Hammarström, Sten; Danielsson, Åke; Hammarström, Marie‐Louise

doi:10.1046/j.1365-2249.2003.02268.x

Cited by 136 publications

(111 citation statements)

References 46 publications

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“…This is consistent with the fact that IL-10 Ϫ/Ϫ mice spontaneously develop colitis (82). IL-10 is overexpressed in patients with active UC, and IL-10 therapy has had success in experimental colitis and IBD treatment (7,96,134). This could be due to the fact that IL-10 stimulates TIMP-1 production as well as reducing secretion of MMP-2 and -9 in in vitro assays, preventing ECM degradation (146).…”

Section: Angiogenic Mediators In Ibd and Experimental Colitissupporting

confidence: 65%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

144

114

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Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 293: G5-G18, 2007. First published April 26, 2007; doi:10.1152/ajpgi.00107.2007.-Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. inflammation; T cells; growth factors; adhesion molecules; antiangiogenesis ANGIOGENESIS PLAYS AN IMPORTANT role in many chronic inflammatory diseases including but not limited to diabetic retinopathy, atherosclerosis, rheumatoid arthritis, hypercholesterolemia, and psoriasis. It has been suggested that the angiogenic components of these diseases contribute to and exacerbate disease conditions (26, 31). Recent findings, both clinical and experimental, indicate that angiogenesis also plays a crucial role in the inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC) (31,37,58,131,155). Development of new vasculature during chronic inflammation may play a negative "pathological" role by contributing to increased inflammatory responses due to dysfunctional new vessel architecture and increases in the recruitment of inflammatory cell types. Importantly, recent data have shown that angiogenic inhibition during chronic inflammatory diseases attenuates further inflammation and disease pathology (31, 37, 51). As such, expanding our knowledge of how pathological angiogenesis occurs during IBD will further our ability to treat patients with these diseases. IBD PathogenesisCD and UC are idiopathic inflammatory disorders of the intestine and/or colon in which patients suffer from rectal bleeding, severe...

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Section: Angiogenic Mediators In Ibd and Experimental Colitissupporting

confidence: 65%

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Chidlow

Shukla²,

Grisham³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

144

114

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“…These results are compatible with the reports about intestinal mucosal lymphocyte of inflammatory bowel disease patients [25][26][27]. We conjecture, on the basis of these findings, that overexpression of Smad7 enables T-cells to activate through blockage of TGF-beta intracellular signaling in tonsillar T-lymphocyte of PPP patients.…”

Section: As Described In Introduction Pustulosis Palmaris Et Plantarsupporting

confidence: 92%

“…In addition, recent study supported that TGF-beta had also important part in the prevention of hyper immune response to indigenous bacteria [24]. On the other hand, in intestinal mucosal T-cells of inflammatory bowel disease (IBD), which are also reported to hypersensitivity to indigenous bacteria as well as PPP, overexpression of Smad7 without alternation of TGF-beta expression has been reported [25][26][27][28]. Because TGF-beta is an inhibitory cytokine against T-cells activation [29], upregulation of Smad7 may leads to unresponsiveness of TGF-beta1, resulting in uncontrolled activation of T-cells and disorder of mucosal immunological tolerance.…”

Section: Introductionmentioning

confidence: 95%

Increase of activated T-cells and up-regulation of Smad7 without elevation of TGF-beta expression in tonsils from patients with pustulosis palmaris et plantaris

Takahara

Kishibe

Nozawa

et al. 2005

Clinical Immunology

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SUMMARYPustulosis palmaris et plantaris (PPP) is known to be skin disease related to tonsillitis, because the pustulosis often become exacerbated during acute tonsillitis and disappears after tonsillectomy. However, etiology of PPP remains unclear. In this study, we investigated the activation of tonsillar T-cell from PPP patients. Furthermore, we analyzed expressions of cytotoxic T-lymphocyte antigen-4 (CTLA4) that is a co-stimulatory molecule for inhibition of T-cell activation and of Smad7 that is a regulatory factor of TGF-beta intracellular signaling. For 47 Japanese patients with PPP who had tonsillectomy, the skin lesion was improved in 87 % of PPP patient at twelve month after tonsillectomy. In quantitative immunohistologic analysis, T-cell nodules on tonsillar tissues from PPP patients were more expanded than those from the patients with obstructive sleep apnea syndrome (OSAS) (p=0.015), and there was a positive correlation between the enlargement and clinical improvement (r=0.422, p=0.021).Flow cytometric analysis showed that the numbers of CD4+CD25+ and CD4+CD29+ cells in tonsils from PPP patients increased significantly compared to those from OSAS patients (p=0.017, p=0.016, respectively). Using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting analyses with CD3+ tonsillar lymphocytes, we found that both expressions of Smad7 mRNA and protein were enhanced in PPP patients compared with OSAS patients (p=0.03, p=0.02, respectively), but expression of TGF-beta mRNA was not different between 2 groups. Although mRNA expression of CTLA4 was reduced in PPP patients compared with OSAS patients (p=0.04), the CTLA4 surface protein expression was not different between 2 groups. These data suggest that helper T-cells are frequently activated in tonsils from PPP patients, and this activation may be related to unresponsiveness of TGF-beta1 by overexpression of Smad7. Such hyper-activation of T-cell may increase the risk of elicitation of self-reactive T-cell, being associated with pathogenesis of PPP.

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“…Tissue biopsy samples were purchased from a commercial source and were thus handled and stored using conventional methods (snap freezing in liquid nitrogen after removal and storage at −80°C for upward of 1 mo). The optimal amount of tissue for detection from these samples was found to be ∼500 μg per electrode; typical colon punch biopsies yield 350 mg of tissue (35). Samples of colorectal carcinoma tissue as well as the adjacent healthy tissue were prepared just as the cultured cell lysate, and showed differential activity with our electrochemical platform.…”

Section: Resultsmentioning

confidence: 99%

Label-free electrochemical detection of human methyltransferase from tumors

Furst

Muren

Hill

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The role of abnormal DNA methyltransferase activity in the development and progression of cancer is an essential and rapidly growing area of research, both for improved diagnosis and treatment. However, current technologies for the assessment of methyltransferase activity, particularly from crude tumor samples, limit this work because they rely on radioactivity or fluorescence and require bulky instrumentation. Here, we report an electrochemical platform that overcomes these limitations for the label-free detection of human DNA(cytosine-5)-methyltransferase1 (DNMT1) methyltransferase activity, enabling measurements from crude cultured colorectal cancer cell lysates (HCT116) and biopsied tumor tissues. Our multiplexed detection system involving patterning and detection from a secondary electrode array combines low-density DNA monolayer patterning and electrocatalytically amplified DNA charge transport chemistry to measure selectively and sensitively DNMT1 activity within these complex and congested cellular samples. Based on differences in DNMT1 activity measured with this assay, we distinguish colorectal tumor tissue from healthy adjacent tissue, illustrating the effectiveness of this two-electrode platform for clinical applications.DNA electrochemistry | methylation detection | electrocatalysis

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Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis

Cited by 136 publications

References 46 publications

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Increase of activated T-cells and up-regulation of Smad7 without elevation of TGF-beta expression in tonsils from patients with pustulosis palmaris et plantaris

Label-free electrochemical detection of human methyltransferase from tumors

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