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 therapeutic potential of flavaglines to promote intestinal epithelial cell homeostasis and to protect against a model of experimental colitis in which inflammation is driven by epithelial ulceration. METHODS:Survival and homeostasis of Caco2-BBE and IEC-6 intestinal epithelial cell lines were measured during treatment with the flavaglines FL3 or FL37 alone and in combination with the proinflammatory cytokines tumor necrosis factor (TNF) α and interferon γ. Wild-type mice were intraperitoneally injected with 0.1 mg/kg FL3 or vehicle once daily for 4 days during dextran sodium sulfate-induced colitis to test the in vivo anti-inflammatory effect of FL3. RESULTS:FL3 and FL37 increased basal Caco2-BBE and IEC-6 cell viability, decreased apoptosis, and decreased epithelial monolayer permeability. FL3 and FL37 inhibited TNFα- and interferon γ-induced nuclear factor kappa B and Cox2 expression, apoptosis, and increased permeability in Caco2-BBE cells. FL3 and FL37 protected against TNFα-induced mitochondrial superoxide generation by preserving respiratory chain complex I activity and prohibitin expression. p38-MAPK activation was essential for the protective effect of FL3 and FL37 on barrier permeability and mitochondrial-derived reactive oxygen species production during TNFα treatment. Mice administered FL3 during dextran sodium sulfate colitis exhibited increased colonic prohibitin expression and p38-MAPK activation, preserved barrier function, and less inflammation. CONCLUSIONS:These results suggest that flavaglines exhibit therapeutic potential against colitis and preserve intestinal epithelial cell survival, mitochondrial function, and barrier integrity.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Han J,Zhao Q,Basmadjian C,Désaubry L,Theiss ALdoi
10.1097/MIB.0000000000000592subject
Has Abstractpub_date
2016-01-01 00:00:00pages
55-67issue
1eissn
1078-0998issn
1536-4844journal_volume
22pub_type
杂志文章abstract:BACKGROUND:Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) presumably caused by dysregulated immune responses to the gut microbiota. Genetic association studies have implicated dozens of chromosomal regions or loci in IBD susceptibility. The next challenge is to explain the indiv...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21887
更新日期:2012-06-01 00:00:00
abstract::The complex and yet unknown etiology of Crohn's disease (CD) might consist of various disease endophenotypes, each of which represent their own pathogenesis. This review focuses on the disease endophenotype linked to polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) protein and on the ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21656
更新日期:2011-11-01 00:00:00
abstract::Anorexia, malnutrition, altered body composition and development of mesenteric obesity are well known features of inflammatory bowel disease (IBD). Recent data suggest that dysregulation of protein secretion by white adipose tissue is involved in these manifestations of patients with IBD. Adipocytes are recently recog...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/01.mib.0000178915.54264.8f
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL is believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known to contribute to intestinal pathology in inflammatory bowel disease, their r...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000731
更新日期:2016-06-01 00:00:00
abstract::The diagnosis of inflammatory bowel disease (IBD) is traditionally based on a combination of clinical, endoscopic, histological, and radiological criteria. However, further testing is needed in cases of diagnostic uncertainty and in predicting disease course. This systematic review focuses on the potential for 10 sero...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21903
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:L-selectin (CD62L) and β(7) integrins are important for trafficking of naive T cells under steady-state conditions. The objectives of this study were to dissect the requirements for T cell-associated CD62L and β(7) integrins during initiation, progression, and regulation of chronic colitis. METHODS:Using th...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e3182a8df0a
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Immunomodulator (IM) treatments in ulcerative colitis (UC) are not curative and carry increased risk of complications, sometimes leading to therapy changes, reduced treatment benefits, and eventual relapse. We assessed patterns of IM utilization and therapy changes, complications, and disease relapse in a re...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000089
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:The Crohn's Disease Activity Index (CDAI) has been criticized for being weakly correlated with bowel inflammation. We assessed correlation between Simple Endoscopic Score for Crohn's Disease (SES-CD) and individual CDAI items stratified by disease location to better understand this relationship. METHODS:We ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz241
更新日期:2020-01-06 00:00:00
abstract:BACKGROUND:According to the Montreal Classification, upper gastrointestinal tract phenotype L4 is uncommon in Caucasian patients with Crohn's disease (CD) but carries excess risk of recurrence. We studied the clinical course of CD in Chinese patients presenting with the L4 phenotype and factors predicting its occurrenc...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20804
更新日期:2009-04-01 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: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:Patients with inflammatory bowel disease (IBD) are more susceptible to mental health problems than the general population; however, temporal trends in psychiatric diagnoses' incidence or prevalence in the United States are lacking. We sought to identify these trends among patients with IBD using national Vet...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz280
更新日期:2020-08-20 00:00:00
abstract:Background:Both muscle-related complaints and elevated serum creatine kinase (CK) levels have been reported in patients with inflammatory bowel disease (IBD) treated with infliximab (IFX), mainly as case reports. The aim of this study was to investigate the effect of IFX therapy on serum CK levels in a cohort of Greek ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy088
更新日期:2018-05-18 00:00:00
abstract::As the frontiers of immunological research expand, new insights into the pathogenesis of long poorly understood diseases, such as inflammatory bowel disease (IBD), are opening up new possible avenues for treatment. Myeloid-derived cells (i.e., monocytes, macrophages, neutrophils, and dendritic cells), long believed to...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000511
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Mesalamine, 5-aminosalicylic acid (5-ASA), is a potent antioxidant and is known to enhance peroxisome proliferator-activated receptor γ activity in the intestine. Our previous studies suggested reduced Phosphoinositide 3-Kinase (PI3K)/β-catenin signaling as a mechanism for 5-ASA chemoprevention in chronic ul...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e318297d741
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy is effective in treating some Crohn's disease (CD) patients and protects mice from colitis induced by dextran sulfate sodium (DSS) administration. However, its mechanisms of action remain elusive. We hypothesized that GM-CSF affects intestinal...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21072
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND:The etiology of ulcerative colitis (UC) and Crohn's disease (CD) involves both genetic and environmental components. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. These studies have also highlighted the presence of genes com...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1097/MIB.0b013e3182810041
更新日期:2013-02-01 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
abstract::We report a case of a 40-year-old woman who had received infliximab for perianal Crohn's disease. After six infusions of infliximab, the patient developed staphylococcal pneumonia resulting in fatal adult respiratory distress syndrome. The case is discussed in the context of the toxicity profile of infliximab. ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200409000-00024
更新日期:2004-09-01 00:00:00
abstract::Focal infection theory posits that periodontal pathobionts play a causal role in initiating or exacerbating diseases. Periodontal disease is a common inflammatory, multifactorial disease of the periodontal tissues. The main factor for inflammation is mature dental plaque with the presence of pathogens in the microbial...
journal_title:Inflammatory bowel diseases
pub_type: 评论,社论
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更新日期:2020-01-06 00:00:00
abstract:BACKGROUND:Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. METHODS:In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:Pharmacologic inhibition or genetic ablation of phosphoinositide 3-kinase gamma (PI3Kγ) has been shown to be protective against experimental colitis. However, the role of PI3Kγ in the resolution phase of colitis remains unexplored. In this study, we assess the effects of genetic knockout of PI3Kγ on the indu...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e31827feb84
更新日期:2013-03-01 00:00:00
abstract:Background:The Crohn's Disease Activity Index (CDAI), a scoring index including patient-reported outcomes (PROs), has known limitations for measuring intestinal inflammatory disease burden. Noninvasive markers of inflammation could prove more accurate than PROs; thus, regulatory authorities are exploring the use of PRO...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1093/ibd/izx018
更新日期:2018-01-18 00:00:00
abstract::Colitis-associated colorectal neoplasia (CRN) is a well-known complication of chronic inflammation of the colon either with ulcerative colitis (UC) or colonic Crohn's disease (CD). Studies have shown that inflammatory bowel disease (IBD) patients have an overall higher risk for colorectal dysplasia and cancer compared...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000685
更新日期:2016-05-01 00:00:00
abstract:Background:Standard outpatient induction dosing of infliximab (IFX) may not be effective in hospitalized ulcerative colitis (UC) patients with higher inflammatory burden and colectomy risk. Our aim was to determine whether initial IFX induction dose affects 30-day colectomy rate and other disease-related outcomes. Met...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izx039
更新日期:2018-02-15 00:00:00
abstract:BACKGROUND:The majority of studies concerning the clinical course and prognosis in ulcerative colitis (UC) are old, retrospective in design, or hospital based. We aimed to identify clinical course and prognosis in a prospective, population-based follow-up study MATERIALS AND METHODS:Patients diagnosed with inflammator...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000225339.91484.fc
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND:Helicobacter pylori infection is associated with a lower risk of chronic autoimmune diseases including inflammatory bowel disease (IBD). H.pylori modulates the gastric immune response, decreasing the local inflammatory response to itself. In mice, chronic Salmonellatyphimurium infection induces colitis simil...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21489
更新日期:2011-06-01 00:00:00
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 ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21851
更新日期:2012-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20851
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Extraintestinal manifestations of Crohn's disease (CD) have not previously included the central nervous system (CNS). Restless legs syndrome (RLS) is a CNS disorder that is either idiopathic or secondary to a number of diseases. The aim of this study was to determine if RLS was associated with CD because bot...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20992
更新日期:2010-02-01 00:00:00