Abstract:
BACKGROUND:The dsRNA-activated protein kinase (PKR) phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), a global regulator of protein synthesis in mammals. In addition, PKR activates several signal transduction pathways including STAT3 and AKT. PKR is activated by a number of inflammatory stimuli that are induced in the inflamed intestine. In this study we intended to determine the role of PKR in colonic epithelial cells during experimental colitis in mice. METHODS:Age- and sex-matched PKR(+/+,+/-) and PKR(-/-) littermate mice were reconstituted with wildtype bone marrow cells and subjected to dextran sodium sulfate (DSS)-induced colitis. RESULTS:PKR(-/-) mice displayed more severe clinical and histological manifestations upon DSS colitis compared with their PKR(+/+,+/-) littermates. In response to DSS colitis, the colonic epithelial cells of PKR(-/-) mice exhibited impaired activation of the unfolded protein response (UPR) signaling, including eIF2α phosphorylation, endoplasmic reticulum (ER) chaperone response, and ER-associated degradation (ERAD) components, as well as antioxidative stress response. In addition, the phosphorylation of STAT3 and AKT, which are protective against epithelial cell death and colonic inflammation, was also impaired in the colonic epithelial cells of PKR(-/-) mice upon DSS colitis. CONCLUSIONS:These data demonstrate that PKR is a physiologically relevant transducer of inflammatory response signaling in colonic epithelial cells. PKR may promote the homeostasis and survival of intestinal epithelial cells (IECs) through eIF2α-mediated UPR activation, as well as the activation of STAT3 and AKT pathways. In the absence of PKR, the survival and proliferation of IECs was impaired, thus exacerbating intestinal inflammation.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Cao SS,Song B,Kaufman RJdoi
10.1002/ibd.22878subject
Has Abstractpub_date
2012-09-01 00:00:00pages
1735-42issue
9eissn
1078-0998issn
1536-4844journal_volume
18pub_type
杂志文章abstract:BACKGROUND:Chronic inflammation in ulcerative colitis (UC) is a sizeable risk factor for colorectal cancer (CRC). Interleukin-13 (IL-13) is elevated in the UC mucosa and may induce dysregulated signaling in neighboring intestinal epithelial cells (IECs) and thus function as a tumorogenic cytokine. METHODS:Expression o...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,收录出版
doi:10.1002/ibd.21133
更新日期:2010-05-01 00:00:00
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::Biologic treatments have revolutionized the way we treat inflammatory bowel disease patients (IBD). Anti-tumor necrosis factor (anti-TNF) antibodies are superior to conventional therapies to achieve sustained remission without steroids and mucosal healing. The objective of IBD treatment has evolved from symptom allevi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1093/ibd/izx098
更新日期:2018-03-19 00:00:00
abstract:BACKGROUND:Inflammatory bowel diseases (IBD) are characterized by intermittent relapses, and their course is heterogeneous and unpredictable. Our aim was to determine the ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease. METHODS:This prospective study enroll...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa183
更新日期:2020-09-18 00:00:00
abstract::Mesalamine has a well-established role in the management of ulcerative colitis. However, its role in the management of Crohn's disease (CD) is less clear. Studies evaluating its therapeutic value in CD have produced both positive and negative results. Meta-analyses have not clarified the situation, possibly because th...
journal_title:Inflammatory bowel diseases
pub_type: 评论,社论
doi:10.1097/01.mib.0000160743.24772.69
更新日期:2005-06-01 00:00:00
abstract::Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn's disease. The immune response in ulcerative colitis is different from the Crohn's disease. Accumulating evidence suggests that IBD results from an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host. Severa...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000477
更新日期:2015-09-01 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:The risk of corticosteroid-associated adverse events can limit the use of systemic corticosteroids. Oral, topically acting, second-generation corticosteroids that deliver drug to the site of inflammation, and biologic therapies, are effective treatment alternatives. The aim of this review was to evaluate the...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000001261
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND:Increased strength of red blood cell (RBC) aggregates are present during the acute inflammatory response and contribute to erythrocyte aggregation and may lead to microvascular dysfunction. Inflammatory bowel diseases (IBDs) are characterized by damage to the bowel wall. This damage may be at least partially...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20838
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Although many genetic variants are identified in association with Crohn's disease (CD), CARD15, IL23R, and ATG16L1 association with CD have been firmly confirmed in Caucasians of European ancestry. The prevalence of CD is rapidly rising in Brazil, where European ancestry is firmly admixed with natives and Af...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20372
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21537
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Fibrostenosis and stricture are well-recognized endpoints in Crohn's disease (CD). We hypothesized that stricturing CD is characterized by eosinophilia and epithelial IL-33. We proposed that eosinophil exposure to IL-33 would perpetuate inflammatory chronicity and subsequent fibrostenosis. METHODS:We perfor...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000512
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:Our goal in this multicentric prospective study was 2-fold: first, to test the diagnostic accuracy of ultrasound, color Doppler imaging (CDI), and contrast-enhanced ultrasound (CEUS) in identifying disease activity in patients with Crohn's disease (CD) compared with endoscopy as the reference standard; and, s...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa134
更新日期:2021-01-01 00:00:00
abstract::Crohn's disease and ulcerative colitis are quite often complicated with manifestations in extraintestinal organs like joints, eye, and skin. Although the etiopathogenesis of these nonmucosal complications remains unsettled, they all share the characteristic feature of inappropriate leukocyte recruitment in nonlymphati...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.3780040210
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:Improving granulocyte function may represent an effective therapy for Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in children with CD. METHODS:This was multicenter, open-label study in 6-16-year-old patients with moderate to severely active CD. Patients received either 4 or 6 ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1002/ibd.21204
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND:Interestingly, Clostridium difficile infection (CDI) worsens the course of inflammatory bowel disease (IBD); however, there is a paucity of data regarding the treatment of CDI in this group of patients. METHODS:This was a prospective, single-blind trial. Children with flare of IBD and CDI were randomly assi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
doi:10.1097/MIB.0000000000001249
更新日期:2017-12-01 00:00:00
abstract:Background:The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) is a challenge. The aim of this study was to investigate a predictive model for differential diagnosis between ITB and CD. Methods:A total of 268 patients who were suspected of having ITB or CD were prospectively recruited be...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy154
更新日期:2018-10-12 00:00:00
abstract:BACKGROUND:Interleukin-13 (IL-13) is a multifunctional cytokine whose net principle action is to diminish inflammatory responses. Dysregulation of IL-13 production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in IBD pathogenesi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200409000-00014
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:Magnetic resonance enteroclysis (MRE) is a recently introduced imaging technique that assesses the small bowel with similar sensitivity and specificity as the fluoroscopically performed conventional enteroclysis. Magnetic resonance imaging colonography (MRC) seems to be a promising technique for polyp assess...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1097/01.mib.0000164022.72729.06
更新日期:2005-04-01 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: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::: Restorative proctocolectomy with ileal pouch-anal anastomosis is the standard surgical treatment modality for patients with ulcerative colitis who require colectomy. There are special issues related to male gender. We performed systemic literature review on the topic, incorporating the experience in our specialized ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000226
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:The aim of this study was to develop a shortened Crohn's Disease Activity Index (CDAI). METHODS:A short CDAI was developed retrospectively using patient-level data from four budesonide clinical trials to select variables from the full CDAI which best predicted health-related quality of life as measured by t...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21400
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Mucosa-associated Escherichia coli are abundant in inflammatory bowel disease (IBD), but whether these bacteria gain intracellular access within the mucosa is uncertain. If E. coli does gain intracellular access, the contribution of bacterial pathogenicity to this requires further elucidation. This study aim...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e3182a38a92
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND:Adipose tissue is recognized as a compartment secreting highly active molecules. Creeping fat represents a characteristic feature of Crohn's disease (CD). Proinflammatory or anti-inflammatory adipose-derived secretory products, now generally called adipocytokines, may play a role in the pathogenesis of CD. ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200606000-00005
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND:Osteoporosis is a well-known complication of Crohn's disease (CD). Osteoprotegerin (OPG) concentration is elevated in patients with CD compared to healthy controls. Long-term infliximab (IFX) maintenance therapy improves the patients' bone mineral density. The effect of IFX on bone metabolism has not yet bee...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1002/ibd.20234
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Glycobiology is an underexplored research area in inflammatory bowel disease (IBD), and glycans are relevant to many etiological mechanisms described in IBD. Alterations in N-glycans attached to the immunoglobulin G (IgG) Fc fragment can affect molecular structure and immunological function. Recent genome-wi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000372
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:The incidence of ulcerative colitis (UC) varies between Western and Eastern ethnicities. A distinct genetic background may play a role in the differences. Until now, very little was known of the UC genetics in Asian populations. Here we performed a haplotype-based analysis of six known UC susceptibility loci...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21652
更新日期:2011-12-01 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::Citrullination is a posttranslational modification of proteins mediated by a specific family of enzymes called peptidylarginine deiminases (PAD). Dysregulation of these enzymes is involved in the etiology of various diseases, from cancer to autoimmune disorders. In inflammatory bowel disease (IBD), data for a role of ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa095
更新日期:2021-01-01 00:00:00