Abstract:
:After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effective alternative. With 2 currently approved drugs (ie, natalizumab, vedolizumab) and several others in phase 3 trials (eg, etrolizumab, ozanimod, anti-MAdCAM-1), the blockade of trafficking molecules has firmly emerged as a new therapeutic era for IBD. We discuss the targets that have been explored in clinical trials: chemokines and its receptors (eg, IP10, CCR9), integrins (eg, natalizumab, AJM300, vedolizumab, and etrolizumab), and its endothelial ligands (MAdCAM-1, ICAM-1). We also discuss a distinct strategy that interferes with lymphocyte recirculation by blocking lymphocyte egress from lymph nodes (small molecule sphingosine-phosphate receptor [S1PR] agonists: fingolimod, ozanimod, etrasimod, amiselimod). Strategies on the horizon include additional small molecules, allosteric inhibitors that specifically bind to the active integrin form and nanovectors that allow for the use of RNA interference in the quest to modulate pro-inflammatory leukocyte trafficking in IBD.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Pérez-Jeldres T,Tyler CJ,Boyer JD,Karuppuchamy T,Bamias G,Dulai PS,Boland BS,Sandborn WJ,Patel DR,Rivera-Nieves Jdoi
10.1093/ibd/izy269subject
Has Abstractpub_date
2019-01-10 00:00:00pages
270-282issue
2eissn
1078-0998issn
1536-4844pii
5079145journal_volume
25pub_type
杂志文章,评审abstract::Gastrointestinal disorders, although clinically heterogeneous, share pathogenic mechanisms, including genetic susceptibility, impaired gut barrier function, altered microbiota, and environmental triggers (infections, social and behavioral factors, epigenetic control, and diet). Gut microbiota has been studied for infl...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000602
更新日期:2016-02-01 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:Clostridium difficile infection (CDI) is a common complication of inflammatory bowel diseases (IBDs) and is associated with worse outcome. Variable rates of colectomy have been reported among IBD complicated by CDI. We conducted a systematic review and meta-analysis of studies to assess the association betwe...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1097/MIB.0000000000000998
更新日期:2017-02-01 00:00:00
abstract:Background:Colorectal cancer (CRC) is a major cause of cancer-related deaths, and tumor-related comorbidities additionally lower life quality and survival. Mutations in the tumor suppressor adenomatous polyposis coli (APC) are associated with sporadic CRC and familial adenomatous polyposis (FAP), which results in the g...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy234
更新日期:2018-10-12 00:00:00
abstract:BACKGROUND:Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences. METHODS:Whole-genome gene expression analys...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e31827eeaa4
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Chronic inflammatory diseases are characterized by massive infiltration of innate and acquired immune cells in inflammatory sites. However, it remains unclear how these cells cooperate in the development of disease. Although bone marrow (BM) is a primary site for hematopoiesis of immune cells except T cells,...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20531
更新日期:2008-11-01 00:00:00
abstract::Crohn's disease is complicated by the development of fibrosis and stricture in approximately 30% to 50% of patients over time. The pathogenesis of fibrostenotic disease is multifactorial involving the activation of mesenchymal cells by cytokines, growth factors, and other mediators released by immune cells, epithelial...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000043
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:Our previous study showed that nephrolithiasis is a common complication in ulcerative colitis patients after ileal pouch anal anastomosis (IPAA). However, the pathogenesis of nephrolithiasis in IPAA patients has not been studied. The aim of this study was to compare urine and serum metabolic compositions in ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001070
更新日期:2017-05-01 00:00:00
abstract::Inflammatory bowel disease is associated with industrialization, and its incidence has increased markedly over time. The prospect of reversing these trends motivates the search for the agent(s) involved. Modernity entails several physical and behavioral modifications that compromise both the photosynthesis of cholecal...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0b013e31828a3b6f
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low-dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)-induced colitis in ra...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.mib.0000174374.83601.86
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND:Under experimental chronic inflammation, tumor necrosis factor (TNF)-alpha plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder wher...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20374
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:The proinflammatory effect of high-fat diet has been observed beyond the cardiovascular system, but there is little evidence to support its role in triggering inflammatory bowel disease. GPx1/2-double-knockout (DKO) mice deficient in 2 intracellular glutathione peroxidases, GPx1 and GPx2, on a C57BL/6 (B6) b...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21317
更新日期:2010-12-01 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::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:BACKGROUND:The risk of suicide is increased among people with inflammatory bowel disease (IBD); however, most of the evidence regarding this association comes from studies of all-cause mortality, with small numbers of people who have committed suicide, or from clinical case reports. The current study examined the assoc...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21298
更新日期:2010-12-01 00:00:00
abstract::Most conventional forms of drug therapy suppress or modify the host immunoinflammatory response and neglect the other contributor to disease pathogenesis-the environmental microflora. Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health. The rationale ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200005000-00007
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND:The women's health aspect of inflammatory bowel disease (IBD) is a newer area of study; childbearing issues have received little attention despite the fact that IBD affects women predominantly during their childbearing years. The aim of this study was to better understand patients' considerations about pregn...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20082
更新日期:2007-05-01 00:00:00
abstract::This review summarizes how interleukin-10 (IL-10)-deficient mice have permitted new insight into the complex interaction between genes and environment underlying pathogenesis of inflammatory bowel disease (IBD). The C57BL/6J strain develops only mild typhlocolitis in response to IL-10 deficiency. In contrast, C3H/HeJB...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200209000-00006
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND:The role of antiviral therapy in patients with ulcerative colitis (UC) with cytomegalovirus (CMV) remains unclear. We therefore performed a systematic review and meta-analysis to assess the association between antiviral therapy and the risk of colectomy. METHODS:Multiple electronic databases were searched s...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1097/MIB.0000000000000489
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:Flavaglines are a family of natural compounds shown to have anti-inflammatory and cytoprotective effects in neurons and cardiomyocytes. Flavaglines target prohibitins as ligands, which are scaffold proteins that regulate mitochondrial function, cell survival, and transcription. This study tested the therapeu...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000592
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:There has been a dramatic increase in investigations on the potential mechanistic role of the intestinal microbiota in various diseases and factors modulating intestinal microbial composition. We recently reported on intestinal microbial shifts after smoking cessation in humans. In this study, we aimed to co...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000129
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:Adverse drug reactions to azathioprine, the prodrug of 6-mercaptopurine, occur in 15%-38% of patients and the majority are not explained by thiopurine-S-methyltransferase (TPMT) deficiency. Azathioprine is known to induce glutathione depletion and consumption of glutathione is greater in cells with high glut...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20004
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:CEACAM1, CEACAM5, and CEACAM6 represent 3 of the CEACAM (carcinoembryonic antigen-related cell adhesion molecule) subfamily members expressed on intestinal epithelial cells (IECs). Deficiency in their expression, as seen in inflammatory bowel disease (IBD), results in the lack of activation of CD8+ regulator...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21023
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Apolipoprotein E (ApoE) mediates potent antiinflammatory and immunomodulatory properties in addition to its roles in regulating cholesterol transport and metabolism. However, its role in the intestine, specifically during inflammation, is largely unknown. METHODS:Mice (C57BL/6 or ApoE-deficient [ApoE-KO] mi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000699
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:Childhood-onset Crohn's disease (CD) might reflect a more severe form of disease. To test this hypothesis we analyzed the long-term natural history of CD in an adult cohort of patients with childhood-onset compared to adult-onset CD. METHODS:We selected 206 childhood-onset CD patients among 2992 adult patie...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21152
更新日期:2010-06-01 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
abstract:BACKGROUND:Vedolizumab is a gut-selective biologic that has shown efficacy in ulcerative colitis (UC) and Crohn's disease (CD). We studied the pharmacokinetics, pharmacodynamics, safety, tolerability, and efficacy of a new formulation of vedolizumab produced by an improved manufacturing process. METHODS:UC patients we...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
doi:10.1002/ibd.21896
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Caspase activation and recruitment domain 3 (CARD3) is a 61-kDa protein kinase. Recent evidence shows the importance of CARD3 in the immune response and inflammatory diseases. To elucidate its impact on inflammatory bowel disease, we studied the effects of the loss of CARD3 in the acute dextran sodium sulfat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000322
更新日期:2015-04-01 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:BACKGROUND:To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). METHODS:A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20044
更新日期:2007-05-01 00:00:00