Abstract:
BACKGROUND:Genetic variants of nucleotide-binding oligomerization domain 2 (NOD2) lead to aberrant microbial recognition and can cause chronic inflammatory diseases in patients with Crohn's disease (CD). METHODS:We utilized gene-specific siRNA mediated knockdown and expression of guanine nucleotide exchange factor H1 (GEF-H1) in wildtype, Rip2-, and Nod2-deficient macrophages, HCT-116 and HEK 293 cells to determine the role of GEF-H1 in NOD2 and Rip2-mediated NF-κB-dependent induction of proinflammatory cytokine expression. Confocal microscopy was used to determine subcellular distribution of GEF-H1, Rip2, and NOD2. RESULTS:We identified GEF-H1 as an unexpected component of innate immune regulation during microbial pattern recognition by NOD2. Surprisingly, GEF-H1-mediated the activation of Rip2 during signaling by NOD2, but not in the presence of the 3020 insC variant of NOD2 associated with CD. GEF-H1 functioned downstream of NOD2 as part of Rip2-containing signaling complexes and was responsible for phosphorylation of Rip2 by Src tyrosine kinase. Rip2 variants lacking the tyrosine target of GEF-H1-mediated phosphorylation were unable to mediate NF-κB activation in Rip2-deficient macrophages and failed to transduce NOD2 signaling. GEF-H1 is required downstream of NOD2 as part of Rip2-containing signaling complexes for the activation of innate immune responses. CONCLUSIONS:GEF-H1 connects tyrosine kinase function to NOD-like receptor signaling and is fundamental to the regulation of microbial recognition by ubiquitous innate immune mechanisms mediated by Rip2 kinase.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Zhao Y,Alonso C,Ballester I,Song JH,Chang SY,Guleng B,Arihiro S,Murray PJ,Xavier R,Kobayashi KS,Reinecker HCdoi
10.1002/ibd.21851subject
Has Abstractpub_date
2012-04-01 00:00:00pages
603-12issue
4eissn
1078-0998issn
1536-4844journal_volume
18pub_type
杂志文章abstract:BACKGROUND:Inflammatory bowel disease (IBD) patients are at increased risk of venous thromboembolism (VTE), which is most pronounced during a disease flare. We explored the cost-effectiveness of pharmacological VTE prophylaxis in an outpatient setting. METHODS:Markov decision analysis was conducted from a societal per...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0b013e31829c01ef
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Obesity is associated with systemic and intestine-specific inflammation and alterations in gut microbiota, which in turn impact mucosal immunity. Nonetheless, a specific role of obesity and its interaction with genetics in the progression of Crohn's disease (CD) is unclear. METHODS:We conducted a cross-sect...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000498
更新日期:2015-10-01 00:00:00
abstract:Background:Sarcopenia is associated with increased morbidity and mortality in oncologic and transplant surgery. It has a high incidence in chronic inflammatory states including inflammatory bowel disease (IBD). The validity of existing data in IBD and of sarcopenia's correlation with surgical outcomes is limited. Meth...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy212
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:We analyzed inflamed mucosal/submucosal layers of ulcerative colitis (UC = 63) and Crohn's colitis (CC = 50), and unexpectedly, we unveiled a pool of free hemoglobin alpha (Hb-α) chain. Patients with colitides have increased reactive oxidative stress (ROS), DNA oxidation products, free iron in mucosa, in pre...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000144
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:There is limited contemporary population-based evidence on adverse birth outcomes and pregnancy-related complications for women with inflammatory bowel disease (IBD). This study provides such estimates of these risks and assesses variation by IBD type and surgical interventions. METHODS:We calculated the pr...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000802
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:The purpose was to estimate the incidence and characteristics of childhood inflammatory bowel disease (IBD) during 2000-2010 in Shanghai, China. METHODS:IBD patients between the ages of 0 and 18 years old were identified by survey of computerized medical information. Relevant data were extracted from their ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0b013e318286f9f2
更新日期:2013-02-01 00:00:00
abstract::Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are poorly understood disorders affecting the intestinal tract. The current model for disease suggests that genetically susceptible patients develop intolerance to gut microflora, and chronic inflammation develops as a result of environmental i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000344
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:The level of inflammatory bowel disease (IBD) training in general gastroenterology fellowship is often insufficient to prepare trainees to deliver advanced IBD care in practice. Advanced IBD fellowships have been developed to fill this training gap, but there is no established curriculum, and significant var...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa177
更新日期:2020-08-20 00:00:00
abstract:BACKGROUND:Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. METHODS:This was a retrospective, observational study of CD pat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21164
更新日期:2010-07-01 00:00:00
abstract::Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.20099
更新日期:2007-05-01 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:Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy. METHODS:This mu...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1093/ibd/izy308
更新日期:2019-03-14 00:00:00
abstract:BACKGROUND:The unavailability of standardized parameters in bowel ultrasonography (US) commonly used in Crohn's disease (CD) and the shortage of skilled ultrasonographers are 2 limiting factors in the use of this imaging modality around the world. The aim of this study is to evaluate interobserver agreement among exper...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1093/ibd/izy091
更新日期:2018-08-16 00:00:00
abstract:BACKGROUND:Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting, and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to pred...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21639
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Infliximab (IFX) infusion may lead to development of anti-IFX antibodies, and subsequent infusion reactions (IRs). The safety of rapid IFX infusion administered over 60 minutes has been under-investigated in children with inflammatory bowel disease. In a multicenter study, the frequency and nature of rapid i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0000000000001259
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:Wiskott-Aldrich syndrome protein-deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which Helicobacter spp. have been implicated in disease pathogenesis. We sought to determi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e318295fd8f
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Several studies suggest an increased risk of venous and arterial thromboembolism (TE) in adults with inflammatory bowel disease (IBD) compared to the general population. We performed a systematic review of studies on incidence and characteristic of TE in children with IBD. METHODS:We searched Medline, LILAC...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21563
更新日期:2011-10-01 00:00:00
abstract::After colectomy and ileal pouch-rectal anastomosis, pouchitis may occur. Pouchitis is a poorly defined condition with unknown etiology. The aim of this study was to develop an animal model of pouchitis. Ileal pouch-rectal anastomosis was created in Lewis and Sprague-Dawley rats. Rats were studied 4 and 8 weeks after s...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-199808000-00003
更新日期:1998-08-01 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:BACKGROUND:This study examines the resources utilization in patients with Crohn's disease (CD) during the year before (Y - 1) and after (Y + 1) starting treatment with adalimumab and the drug's efficiency. METHODS:Observational, multicenter, prospective cohort study of patients with CD naive to biological drugs. The p...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1097/MIB.0000000000000413
更新日期:2015-07-01 00:00:00
abstract::: Primary nonresponse and primary nonremission are important limitations of tumor necrosis factor (TNF) antagonists, occurring in 10% to 40% and 50% to 80% of patients with inflammatory bowel disease, respectively. The magnitude of primary nonresponse differs between phase III clinical trials and cohort studies, indic...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000202
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Microbiota is most likely essential in the pathogenesis of Crohn's disease (CD). Fecal diversion after ileocecal resection (ICR) protects against CD recurrence, whereas infusion of fecal content triggers inflammation. After ICR, the majority of patients experience endoscopic recurrence in the neoterminal ile...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa107
更新日期:2021-01-01 00:00:00
abstract:Background:Vitamin D3 and vitamin D receptor (VDR) are involved in the pathogenesis of inflammatory bowel disease (IBD) and bacterial infection. Claudin-2 is a junction protein that mediates paracellular water transport in epithelia. Elevation of Claudin-2 is associated with active IBD. However, VDR involved in epithel...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy292
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an obje...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000376
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis fo...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001208
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Portal vein thrombosis (PVT) is a poorly described complication of inflammatory bowel disease (IBD). We sought to better characterize presentations, compare treatments, and assess outcomes in IBD-related PVT. METHODS:We conducted a retrospective investigation of IBD-related PVT at our institution. Multivari...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa053
更新日期:2021-01-19 00:00:00
abstract:BACKGROUND:Acute pancreatitis has occasionally been associated with Crohn's disease (CD), but whether a causal association exists remains unclear. We sought to determine the frequency of etiologies in a consecutive series of patients with CD with acute pancreatitis. METHODS:A centralized diagnostic index was used to i...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.mib.0000186485.30623.ad
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Chronic ulcerative colitis (UC) is associated with an increased colorectal cancer risk which may be secondary to repetitive mucosal injury. Both epigenetic methylation and the classic adenoma-to-carcinoma sequence have been implicated in this malignant transformation, but the underlying molecular mechanisms ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21526
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Tumor necrosis factor alpha (TNFalpha) plays a central role in the pathology of T helper 1-mediated colitis such as Crohn's disease; however, the role of its 2 receptors in mediating pathology has not been fully explored. METHODS:Trinitrobenzene sulfonic acid colitis was used to induce colitis in mice lacki...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.mib.0000163698.34592.30
更新日期:2005-06-01 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