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Condition: Inflammatory Bowel Disease

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Total 147 results found since Jan 2013.

Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway
Abstract: Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We recently reported the identification of isorhamnetin as an activator of the human pregnane X receptor (PXR), a known target for abrogating inflammation in inflammatory bowel disease (IBD). The current study investigated the role of isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced IBD. Using two different models (ulcerative colitis like and Crohn's disease like) of experimental IBD in mice, we demonstrated that isorhamnetin abrogated inflammation through inhibiting the activity of myeloperoxidase, the leve...
Source: The Journal of Nutritional Biochemistry - May 9, 2014 Category: Biochemistry Authors: Wei Dou, Jingjing Zhang, Hao Li, Sandhya Kortagere, Katherine Sun, Lili Ding, Gaiyan Ren, Zhengtao Wang, Sridhar Mani Tags: Research Articles Source Type: research

Regulators of NOD2-induced IL-8 Secretion Signal Transduction
NOD2 encodes an intracellular multidomain pattern recognition receptor that is the strongest known genetic risk factor in the pathogenesis of Crohn disease (CD), a chronic relapsing inflammatory disorder of the intestinal tract. NOD2 functions as a sensor for bacterial cell wall components and activates proinflammatory and antimicrobial signaling pathways. Here, using a genome-wide small interfering RNA (siRNA) screen, we identify numerous genes that regulate secretion of the proinflammatory cytokine IL-8 in response to NOD2 activation. Moreover, many of the identified IL-8 regulators are linked by protein-protein interact...
Source: Journal of Biological Chemistry - October 9, 2014 Category: Chemistry Authors: Warner, N., Burberry, A., Pliakas, M., McDonald, C., Nunez, G. Tags: Immunology Source Type: research

Abstract 5358: IL-4/IL-13 induce Duox2/DuoxA2 expression and reactive oxygen production in human pancreatic and colon cancer cells
NADPH oxidase (NOX)-derived reactive oxygen species (ROS) contribute significantly to inflammation-associated carcinogenesis. Expression of dual oxidase 2 (Duox2), one of seven members of the NOX gene family, is up-regulated in inflammatory bowel disease, chronic pancreatitis, and in many human malignancies including carcinomas of the prostate, lung, and breast. Previously, we demonstrated that Stat1 and/or NF-κB play a critical role in modulating the enhanced expression of Duox2, and its cognate maturation factor DuoxA2, by IFN-γ and lipopolysaccharide in human pancreatic cancer cells. This cytokine-mediated increase in...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Wu, Y., Doroshow, J. H. Tags: Carcinogenesis Source Type: research

Differential regulation of interleukin-8 and human beta-defensin 2 in Pseudomonas aeruginosa -infected intestinal epithelial cells
Conclusions: The P. aeruginosa-induced antimicrobial peptide in IECs continuously protect the host against prolonged infection, while modulation of proinflammatory responses prevents the host from the detrimental effects of overwhelming inflammation. Thus, P. aeruginosa-induced innate immunity in IECs represents a host protective mechanism, which may provide new insight into the pathogenesis of inflammatory bowel diseases.
Source: BMC Microbiology - November 30, 2014 Category: Microbiology Authors: Fu-Chen Huang Source Type: research

PAR2 Reduces Colonic Epithelial Apoptosis Molecular Bases of Disease
Mucosal biopsies from inflamed colon of inflammatory bowel disease patients exhibit elevated epithelial apoptosis compared with those from healthy individuals, disrupting mucosal homeostasis and perpetuating disease. Therapies that decrease intestinal epithelial apoptosis may, therefore, ameliorate inflammatory bowel disease, but treatments that specifically target apoptotic pathways are lacking. Proteinase-activated receptor-2 (PAR2), a G protein-coupled receptor activated by trypsin-like serine proteinases, is expressed on intestinal epithelial cells and stimulates mitogenic pathways upon activation. We sought to determi...
Source: Journal of Biological Chemistry - December 4, 2014 Category: Chemistry Authors: Iablokov, V., Hirota, C. L., Peplowski, M. A., Ramachandran, R., Mihara, K., Hollenberg, M. D., MacNaughton, W. K. Tags: Cell Biology Source Type: research

Vacuolar protein sorting 4B regulates apoptosis of intestinal epithelial cells via p38 MAPK in Crohn's disease.
In this study, we reported for the first time that VPS4B was over-expressed in intestinal epithelial cell (IECs) of patients with CD. In TNBS-induced mouse colitis models, we observed the up-regulation of VPS4B was accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and phosphorylated p38 in colitis IECs. Co-localization of VPS4B and active caspase-3 in IECs of the TNBS group further indicated the possible involvement of VPS4B in IEC apoptosis. Employing the TNF-α-treated HT29 cells as an in vitro IEC apoptosis model, we confirmed the positive correlation of VPS4B with caspase...
Source: Experimental and Molecular Pathology - December 20, 2014 Category: Pathology Authors: Zhang D, Wang L, Yan L, Miao X, Gong C, Xiao M, Ni R, Tang Q Tags: Exp Mol Pathol Source Type: research

Citrus nobiletin ameliorates experimental colitis by reducing inflammation and restoring impaired intestinal barrier function
Conclusion: Nobiletin exerted anti‐inflammatory effects in TNBS‐induced colitis through the down‐regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX‐2) expression. Nobiletin restored barrier function, which had been damaged after TNBS administration, through the inhibition of the Akt–NF‐κB–MLCK pathway.This article is protected by copyright. All rights reserved
Source: Molecular Nutrition and Food Research - February 1, 2015 Category: Food Science Authors: Yongjian Xiong, Dapeng Chen, Changchun Yu, Bochao Lv, Jinyong Peng, Jingyu Wang, Yuan Lin Tags: Research Article Source Type: research

TNF-α inhibitor protects against myocardial ischemia/reperfusion injury via Notch1 mediated suppression of oxidative/nitrative stress.
This study aims to determine the involvement of TNF-a inhibitor with Notch1 in MI/R and delineate the related mechanism. Notch1 specific small interfering RNA (siRNA, 20μg) or Jagged1 (a Notch ligand, 12μg) was delivered through intramyocardial injection. 48h after injection, mice received 30min of myocardial ischemia followed by 3h (for cell apoptosis and oxidative/nitrative stress) and 24h (for infarct size and cardiac function) of reperfusion. 10min before reperfusion, mice randomly received intraperitoneal injection of vehicle, Etanercept, diphenyleneiodonium, 1400W or EUK134. Finally, downregulation of Notch1 signif...
Source: Free Radical Biology and Medicine - February 10, 2015 Category: Biology Authors: Pei H, Song X, Peng C, Tan Y, Li Y, Li X, Ma S, Wang Q, Huang R, Yang D, Li, Gao E, Yang Y Tags: Free Radic Biol Med Source Type: research

A Cell Type-Specific Role of Protein Tyrosine Phosphatase Non-Receptor Type 2 in Regulating ER Stress Signalling
Conclusions: Whereas the knockdown of PTPN2 made THP-1 cells more susceptible to ER stress, PTPN2 deficiency reduced ER stress responses in HT-29 IECs. This suggests that PTPN2 regulates adaptation to ER stress in a cell type-specific manner.Digestion 2015;91:248-256
Source: Digestion - March 25, 2015 Category: Gastroenterology Source Type: research

Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation
In this study, we reported for the first time that ESE1/ELF3 was over-expressed in intestinal epithelial cells (IECs) of patients with UC. In DSS-induced colitis mouse models, we observed the up-regulation of ESE1/ELF3 accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and NF-κB activation indicators [phosphorylated NF-κB p65 subunit (p-p65) and p-IκB] in colitis IECs. Increased co-localization of ESE1/ELF3 with active caspase-3 (and p-p65) in IECs of the DSS-induced colitis group further indicated the possible involvement of ESE1/ELF3 in NF-κB-mediated IEC apoptosis in UC...
Source: Immunologic Research - April 30, 2015 Category: Allergy & Immunology Source Type: research

The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation
Conclusion Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that piperine may contribute to prevention or reduction of colonic inflammation. Graphical abstract
Source: Journal of Ethnopharmacology - May 18, 2015 Category: Drugs & Pharmacology Source Type: research

Short- and long-term regulation of intestinal Na+/H+ exchange by toll-like receptors TLR4 and TLR5.
CONCLUSIONS AND IMPLICATIONS: Activation of TLR4 and TLR5 exerts marked inhibition of NHE1 activity in intestinal epithelial cells. Transduction mechanisms set into motion during TLR4-mediated and long-term TLR5-mediated inhibition of NHE1 activity involves AC3, PKA, PLC and PKC. However, short- and long-term TLR4 activation and TLR5 activation might use different signalling pathways. The physiological alterations upon IEC described here may be useful in the development of better IBD therapeutics. PMID: 26294670 [PubMed - as supplied by publisher]
Source: Am J Physiol Gastroi... - August 20, 2015 Category: Gastroenterology Authors: Cabral JM, Gracio D, Soares-da-Silva P, Magro F Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Increased IGF-IEc Expression and Mechano-Growth Factor Production in Intestinal Muscle of Fibrostenotic Crohn's Disease and Smooth Muscle Hypertrophy.
Abstract The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression, IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. MGF derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were i...
Source: Am J Physiol Gastroi... - October 1, 2015 Category: Gastroenterology Authors: Li C, Vu K, Hazelgrove K, Kuemmerle JF Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Short- and long-term regulation of intestinal Na+/H+ exchange by Toll-like receptors TLR4 and TLR5
In this study, we evaluated the activity and expression of Na+/H+ exchanger (NHE) subtypes in T84 intestinal epithelial cells during Toll-like receptor 4 (TLR4) activation by monophosphoryl lipid A and TLR5 by flagellin. NHE activity and intracellular pH were evaluated by spectrofluorescence. Additionally, kinase activities were evaluated by ELISA, and siRNA was used to specifically inhibit adenylyl cyclase (AC). Monophosphoryl lipid A (MPLA) (0.01–50.00 μg/ml) and flagellin (10–500 ng/ml) inhibited NHE1 activity in a concentration-dependent manner (MPLA short term –25.2 ± 5.0%, long term &ndash...
Source: AJP: Gastrointestinal and Liver Physiology - October 15, 2015 Category: Gastroenterology Authors: Cabral, J. M., Gracio, D., Soares-da-Silva, P., Magro, F. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy
The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF p...
Source: AJP: Gastrointestinal and Liver Physiology - December 1, 2015 Category: Gastroenterology Authors: Li, C., Vu, K., Hazelgrove, K., Kuemmerle, J. F. Tags: HORMONES, NEUROTRANSMITTERS, GROWTH FACTORS, RECEPTORS, AND SIGNALING Source Type: research