Abstract:
BACKGROUND:Gliotoxin, a fungal metabolite, has been known to show strong immunosuppressive properties, although its mechanisms are not completely understood. In this report, the authors investigated the mechanism whereby gliotoxin has anti-inflammatory properties in vitro and in trinitrobenzene sulfonic acid-induced colitis. MATERIALS AND METHODS:Body weight, histological scores, and myeloperoxidase activity were evaluated in trinitrobenzene sulfonic acid colitis. Nuclear factor-kappaB (NF-kappaB) p65, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-12, and intercellular adhesion molecule-1 were detected by immunohistochemical staining. IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Heme oxygenase-1 (HO-1) expression and I-kappaB degradation were analyzed by Western blot. RESULTS:Pretreatment of human epithelial HT-29 cells with gliotoxin significantly blocked the I-kappaB degradation and NF-kappaB p65 nuclear translocation induced by tumor necrosis factor-alpha or IL-1beta; these were parallel with the inhibition of IL-8 secretion and intercellular adhesion molecule-1 expression in the same cells. Interestingly, gliotoxin induced HO-1 in HT-29 cells and, in turn, inhibition of HO-1 activity by a zinc protoporphyrin IX reversed the effects of gliotoxin in terms of I-kappaB degradation, intercellular adhesion molecule-1 expression, and IL-8 production. In trinitrobenzene sulfonic acid colitis, gliotoxin administration significantly improved the clinical and histopathological symptoms. Notably, gliotoxin also induced HO-1 in the colonic mucosa and zinc protoporphyrin IX reversed the protective effects of gliotoxin in trinitrobenzene sulfonic acid colitis. CONCLUSIONS:These results demonstrate for the first time that the anti-inflammatory actions mediated by gliotoxin include HO-1 induction and the subsequent blockade of NF-kappaB-dependent signaling pathways in vitro and in vivo. The current results also demonstrate that gliotoxin may be an effective agent for the treatment of diseases characterized by mucosal inflammation.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Jun CD,Kim Y,Choi EY,Kim M,Park B,Youn B,Yu K,Choi KS,Yoon KH,Choi SC,Lee MS,Park KI,Choi M,Chung Y,Oh Jdoi
10.1097/01.ibd.0000225340.99108.8asubject
Has Abstractpub_date
2006-07-01 00:00:00pages
619-29issue
7eissn
1078-0998issn
1536-4844pii
00054725-200607000-00012journal_volume
12pub_type
杂志文章abstract::Dendritic cells (DCs) play a key role in discriminating between commensal microorganisms and potentially harmful pathogens and in maintaining the balance between tolerance and active immunity. The regulatory role of DC is of particular importance in the gut where the immune system lies in intimate contact with the hig...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21247
更新日期:2010-10-01 00:00:00
abstract::The limited efficacy of standard medical therapies for inflammatory bowel diseases has resulted in a continuing search for alternative treatments. Growth hormone (GH) has shown to have mutagenic and proliferative effects on intestinal cells. This study was designed to identify the effect of growth hormone on trinitrob...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200403000-00008
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:A notable proportion of patients with inflammatory bowel disease (IBD) are switched from infliximab (IFX) to adalimumab (ADL). We investigated if immunogenicity of IFX influenced immunogenicity and clinical outcomes of later ADL therapy. METHODS:Single-center cohort study including all patients with IBD ass...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1097/MIB.0000000000000138
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:The clinical implication of Clostridium difficile infection (CDI) in patients with ileal pouch-anal anastomosis (IPAA) for underlying inflammatory bowel disease (IBD) has not been well studied. This study was designed to investigate the cumulative incidence, risk factors, and outcome of CDI in patients with ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1097/MIB.0b013e318280fcb9
更新日期:2013-02-01 00:00:00
abstract::Corticosteroids are considered a drug of choice for the treatment of patients with moderately to severely active Crohn's disease (CD), an inflammatory bowel disease characterized by chronic recurrent flares of disease activity. However, among patients receiving corticosteroid therapy for induction of remission, 20% ha...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.3780070506
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND AND AIMS:Ulcerative colitis (UC) is a form of inflammatory bowel disease, and antibodies against tumor necrosis factor (anti-TNF) are used for treatment. Many patients are refractory or lose response to anti-TNF, and predicting response would be an extremely valuable clinical tool. Unlike most biomarkers, cy...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy358
更新日期:2019-02-21 00:00:00
abstract:BACKGROUND:The mechanisms responsible for the pathogenesis of peripheral arthropathies (PA) in Crohn's disease (CD) are largely unknown, although many studies indicate that genetic and environmental factors are likely to contribute to risk. METHODS:Because variants in the Fc receptor-like 3 (FcRL3) gene have recently ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1002/ibd.20895
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:The cumulative incidence of colectomy and the impact of 5-aminosalicylates (5-ASA), azathioprine, and antitumor necrosis factor (TNF) treatment on the long-term need for surgery are unknown in ulcerative colitis (UC) in the era of biologics. METHODS:This was an observational study of a referral center cohor...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21932
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:The hygiene hypothesis suggests an inverse relationship between the incidence of parasitic infections and chronic inflammatory bowel diseases (IBD). We investigated the therapeutic potential of Schistosoma mansoni and Ancylostoma caninum soluble proteins on experimental colitis in mice. METHODS:Colitis was ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20787
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:The clinical presentation of the inflammatory bowel diseases (IBD) is extremely heterogenous and is characterized by various extraintestinal manifestations and complications (EIM). Increasing genetic insight for IBD and EIM shows multiple shared susceptibility loci. We hypothesize that, next to these overlap...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000032
更新日期:2014-06-01 00:00:00
abstract:BACKGROUND:Endoscopic balloon dilation (EBD) is widely used to manage Crohn's disease-associated strictures. However, most studies of the safety and efficacy are small and heterogenous. We performed a combined analysis of published studies and evaluated 676 comprehensive individual participant data sets to determine th...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1097/MIB.0000000000000988
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVES:Studies aimed at establishing which characteristics of patients with ulcerative proctitis could be predictive of the extension of inflammation have failed to provide conclusive results. The aim of the study was to evaluate the prognostic role of clinical and therapeutic parameters in patients with proctitis....
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200411000-00006
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Toll-like receptor 5 (TLR5) is implicated in the innate and adaptive immune responses that are associated with inflammatory bowel disease (IBD). In humans TLR5 is expressed on CD4(+) T cells and costimulation with flagellin potentiates effector and regulatory T cell responses. The aim of this study was to de...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21738
更新日期:2012-01-01 00:00:00
abstract::The aim of this study was to describe the clinical course of Crohn's disease (CD) in a well-defined, homogeneous groups of patients. A total of 480 patients with CD were followed up from diagnosis up to 20 years. Definitions of patient subgroups were made according to the Vienna Classification. Markov chain analysis w...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200111000-00005
更新日期:2001-11-01 00:00:00
abstract:BACKGROUND:We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection. MATERIALS AND METHODS:Wildtype (WT) and DPIV(-/-) mice consumed 2% DSS ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21241
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel disease (IBD) has a remitting and relapsing disease course; however, relatively little is understood regarding how inflammatory damage in acute colitis influences the microbiota, epithelial barrier, and immune function in subsequent colitis. METHODS:Mice were administered trinitrobenzene ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz011
更新日期:2019-06-18 00:00:00
abstract:BACKGROUND:The dinitrofluorobenzene/dinitrosulfonic acid (DNFB/DNS) model was originally described as an experimental model of intestinal inflammation resembling human ulcerative colitis (UC). Due to the absence of acceptable UC experimental models for pharmacological preclinical assays, here we examine the immune resp...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21586
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Recent animal studies and clinical trials suggest that thiazolidinediones, a class of oral antidiabetic agents, are efficacious in reducing inflammation, yet no studies have evaluated their effectiveness in preventing flares. We examined the association between thiazolidinedione use and ulcerative colitis (U...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21348
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:A high-fat diet is a risk factor for the development of inflammatory bowel disease (IBD) in humans. Deoxycholate (DOC) is increased in the colonic contents in response to a high-fat diet. Thus, an elevated level of DOC in the colonic lumen may play a role in the natural course of development of IBD. METHODS...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000209789.14114.63
更新日期:2006-04-01 00:00:00
abstract:Background:Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods:We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izy014
更新日期:2018-03-19 00:00:00
abstract:BACKGROUND:Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/01.mib.0000158386.25660.1e
更新日期:2005-05-01 00:00:00
abstract:BACKGROUND:The aim of this study was to assess the clinical benefit and tolerability of adalimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF), in patients with ulcerative colitis (UC). METHODS:Patients with active UC, including those who had lost response or developed intolerance to the chimeric...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20924
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Recent studies have suggested that the downregulation of pregnane X receptor (PXR) may contribute to the susceptibility and exacerbation of Crohn's disease (CD). Because bile acid malabsorption is one of the features of CD and bile acids are potential activators of PXR, we explored the relationship between b...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e318281f423
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:Patients with Crohn's disease (CD) with small bowel strictures are at risk of surgery. Double-balloon enteroscopy (DBE) can evaluate the status of the small intestine, and retrograde contrast through the scope enables the surgeon to obtain information beyond the reach of the scope. This study aimed to examin...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001175
更新日期:2017-12-01 00:00:00
abstract::An interleukin (IL)-10 family cytokine, IL-22 is characterized by several unique biological properties, including 1) the target restricted to innate cells; 2) the distinct expression pattern between large and small intestines; 3) alteration of the cellular source depending on several factors; 4) the dual abilities to ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.22929
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:The early molecular changes preceding the onset of mucosal inflammation in colitis and their temporal relationship with gut permeability remain poorly defined. This study investigated functional and transcriptomic changes in mdr1a(-/-) mice lacking the intestinal transporter P-glycoprotein, which develop col...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20375
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Endoscopic balloon dilation (EBD) is an effective method for treating stricture-related obstruction in Crohn's disease. We aimed to identify factors predictive of successful avoidance of surgery, including endoscopic features, in patients undergoing balloon dilation. METHODS:We performed a retrospective rev...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001181
更新日期:2017-10-01 00:00:00
abstract::Inflammatory bowel diseases are chronic intestinal inflammatory diseases thought to reflect a dysregulated immune response. Although antibody-based inhibition of tumor necrosis factor-α (TNF-α) has provided relief to many inflammatory bowel diseases patients, these therapies are either ineffective in a patient subset ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000442839.28664.75
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:A novel family of proton-sensing G protein-coupled receptors, including OGR1, GPR4, and TDAG8, was identified to be important for physiological pH homeostasis and inflammation. Thus, we determined the function of proton-sensing OGR1 in the intestinal mucosa. MTEHODS:OGR1 expression in colonic tissues was in...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000375
更新日期:2015-06-01 00:00:00
abstract::Ulcerative colitis and Crohn's disease both confer an increased risk of developing colorectal cancer. The use of 5-aminosalicylate as a remission-inducing agent has been long accepted. Its use as a potential chemoprophylactic agent has been proposed and is used by some practitioners. This review examines the most rece...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.20186
更新日期:2007-10-01 00:00:00