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Expression of human REG family genes in inflammatory bowel disease and their molecular mechanism
AbstractThe pathophysiology of inflammatory bowel disease (IBD) reflects a balance between mucosal injury and reparative mechanisms. Some regenerating gene (Reg) family members have been reported to be expressed in Crohn ’s disease (CD) and ulcerative colitis (UC) and to be involved as proliferative mucosal factors in IBD. However, expression of all theREG family genes in IBD is still unclear. Here, we analyzed expression of all theREG family genes (REGI α,REGI β,REG III,HIP/PAP, andREG IV) in biopsy specimens of UC and CD by real-time RT-PCR.REG I α,REG I β, andREG IV genes were overexpressed in CD samples.REG IV ge...
Source: Immunologic Research - January 29, 2019 Category: Allergy & Immunology Source Type: research

MMP-9-induced increase in intestinal tight junction permeability is mediated by P38 kinase signaling pathway activation of Myosin Light Chain Kinase gene.
Abstract Matrix Metalloproteinase-9 (MMP-9) has been implicated to be an important pathogenic factor in inflammatory bowel disease (IBD). MMP-9 is markedly elevated in intestinal tissue of patients with IBD, and IBD patients have a defective intestinal tight junction (TJ) barrier manifested by an increase in intestinal permeability. The loss of intestinal barrier function is a contributing factor in the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The purpose of this study was to investigate the effect of MMP-9 on intestinal epithelial TJ barrier and to ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 13, 2018 Category: Physiology Authors: Al-Sadi R, Youssef M, Rawat M, Guo S, Dokladny K, Haque M, Watterson DM, Ma TY Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

1,25 ‑Dihydroxyvitamin D regulates macrophage polarization and ameliorates experimental inflammatory bowel disease by suppressing miR-125b.
This study aimed to explore whether 1,25(OH)2D3 modulates macrophage polarization in inflammation. Peripheral blood mononuclear cells and colitis mice were treated with 1,25(OH)2D3. Macrophages were transfected with siRNA-vitamin D receptor (VDR) or miR-125b mimic or inhibitor, and 1,25(OH)2D3-pretreated colitis mice were injected with a miR-125b agomir. The distribution of macrophage subsets and macrophage subtype characteristics was analyzed. As expected, 1,25(OH)2D3 transformed lipopolysaccharide-induced M1 macrophages to the M2 subset, downregulated tumor necrosis factor-α and interleukin (IL)-6 expression and interfe...
Source: International Immunopharmacology - December 9, 2018 Category: Allergy & Immunology Authors: Zhu X, Zhu Y, Li C, Yu J, Ren D, Qiu S, Nie Y, Yu X, Xu X, Zhu W Tags: Int Immunopharmacol Source Type: research

Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation
Publication date: January 2019Source: Molecular Immunology, Volume 105Author(s): Chu-Tian Mai, Mei-Mei Wu, Chun-Li Wang, Zi-Ren Su, Yuan-Yuan Cheng, Xiao-Jun ZhangAbstractActivation of NLRP3 inflammasomes is crucial in the pathological process of Ulcerative colitis (UC), which could be negatively regulated by PINK1/Parkin-driven mitophagy. Palmatine is a herb derived isoquinoline alkaloid with potent anti-inflammatory and anti-bacteria activities. In present study, we evaluated the effect of palmatine on dextran sulfate sodium (DSS)-induced mice colitis and examined whether its effect is exerted by promoting mitophagy-medi...
Source: Molecular Immunology - November 28, 2018 Category: Allergy & Immunology Source Type: research

Molecules, Vol. 23, Pages 2884: Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis
Tae-Bong Kang Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis fac...
Source: Molecules - November 5, 2018 Category: Chemistry Authors: Eun-Jung In Yuno Lee Sushruta Koppula Tae-Yeon Kim Jun-Hyuk Han Kwang-Ho Lee Tae-Bong Kang Tags: Article Source Type: research

Transforming growth factor β1-induced collagen production in myofibroblasts is mediated by reactive oxygen species derived from NADPH oxidase 4.
In this study, we examined the role of NOX4 in collagen production by intestinal myofibroblasts stimulated with transforming growth factor (TGF)-β1. Using LmcMF cells, an intestinal subepithelial myofibroblast (ISEMF) line, we first examined the induction of collagen production by TGF-β1. Subsequently, we investigated the role of NOX4 in TGF-β1-induced collagen I production in these cells using SB525334 (an SMAD2/3 inhibitor), diphenyleneiodonium (an NOX inhibitor), and Nox4 small interfering RNA (siRNA). Production of collagen was assessed with Sirius red staining, and Nox4 expression was measured by quantitative real-...
Source: Biochemical and Biophysical Research communications - October 23, 2018 Category: Biochemistry Authors: Hotta Y, Uchiyama K, Takagi T, Kashiwagi S, Nakano T, Mukai R, Toyokawa Y, Yasuda T, Ueda T, Suyama Y, Murakami T, Tanaka M, Majima A, Doi T, Hirai Y, Mizushima K, Morita M, Higashimura Y, Inoue K, Fukui A, Okayama T, Katada K, Kamada K, Handa O, Ishikawa Tags: Biochem Biophys Res Commun Source Type: research

Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells.
In conclusion, OXY increases NAD+ levels, resulting in the stimulation of MUC2 expression in LS 174T cells. These findings present a novel role for NAD+ in stimulation of MUC2 expression. PMID: 29935245 [PubMed - as supplied by publisher]
Source: Food and Chemical Toxicology - June 20, 2018 Category: Food Science Authors: Hwang D, Jo H, Ma SH, Lim YH Tags: Food Chem Toxicol Source Type: research

Oregonin inhibits inflammation and protects against barrier disruption in intestinal epithelial cells.
CONCLUSION: The findings of this study suggest that oregonin is a potential candidate for treatment of IBD by preventing mucosal inflammation and barrier disruption. PMID: 29655054 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - April 11, 2018 Category: Allergy & Immunology Authors: Chi JH, Seo GS, Lee SH Tags: Int Immunopharmacol Source Type: research

MicroRNA-146a-5p attenuates visceral hypersensitivity through targeting chemokine CCL8 in the spinal cord in a mouse model of colitis.
In this study, we aimed to explore the potential role of miR-146a-5p (the mature form of miR-146a) in a mouse model of colitis induced by intracolonic injection of trinitrobenzene sulfonic acid (TNBS). We found that induction of colitis resulted in visceral hyperalgesia manifested by a decreased pain threshold to colorectal distension and upregulation of miR-146a-5p expression in the lumbosacral spinal cord. In situ hybridization and immunohistochemistry results showed that miR-146a-5p was colocalized with neuronal marker NeuN, but not with astrocytic marker GFAP or microglial marker IBA-1. Dual-luciferase reporter assay s...
Source: Brain Research Bulletin - March 14, 2018 Category: Neurology Authors: Lu Y, Cao DL, Zhao LX, Han Y, Zhang YL Tags: Brain Res Bull Source Type: research

Hypoxia induces production of citrullinated proteins in human fibroblast ‐like synoviocytes through regulating HIF1α
This article is protected by copyright. All rights reserved.
Source: Scandinavian Journal of Immunology - February 1, 2018 Category: Allergy & Immunology Authors: Ruohan Yu, Changhong Li, Lin Sun, Leilei Jian, Zhenzhen Ma, Jinxia Zhao, Xiangyuan Liu Tags: Regular Article Source Type: research

4 co-delivery of tnf- α sirna and il-22 via a nanoparticle-in-hydrogel system exerts synergistic therapeutic effects against ulcerative colitis
Combination therapy is an emerging approach for treating ulcerative colitis (UC). During the development of UC, TNF- α acts as the major pro-inflammatory cytokine while interleukin-22 (IL-22) plays an important role in preventing mucosal damage. In the present study, we loaded TNF-α siRNA (siTNF) into galactosylated polymeric nanoparticles (NPs). The resultant Gal-siTNF-NPs had a desirable diameter (～261 nm), narrow size distribution and a slightly negative zeta potential (～‒12 mV). These NPs successful mediated the targeted delivery of siTNF to macrophages and efficiently inhibited the expression of TNF-α.
Source: Gastroenterology - January 1, 2018 Category: Gastroenterology Authors: Bo Xiao, Emilie Viennois, Tim L. Denning, Didier Merlin Tags: Clinical and Research Challenges Source Type: research

Lipopolysaccharide-Induced Increase in Intestinal Epithelial Tight Permeability Is Mediated by Toll-Like Receptor 4/Myeloid Differentiation Primary Response 88 (MyD88) Activation of Myosin Light Chain Kinase Expression.
Abstract Lipopolysaccharides (LPSs) are a major component of the Gram-negative bacterial cell wall and play an important role in mediating intestinal inflammatory responses in inflammatory bowel disease. Although recent studies suggested that physiologically relevant concentrations of LPS (0 to 1 ng/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability, the mechanisms that mediate an LPS-induced increase in intestinal TJ permeability remain unclear. Herein, we show that myosin light chain kinase (MLCK) plays a central role in the LPS-induced increase in TJ permeability. Filter-grown Caco-...
Source: The American Journal of Pathology - November 22, 2017 Category: Pathology Authors: Nighot M, Al-Sadi R, Guo S, Rawat M, Nighot P, Watterson MD, Ma TY Tags: Am J Pathol Source Type: research

Epigenetic Modulation of Intestinal Na(+)/H(+) Exchanger-3 Expression.
Abstract Na(+)/H(+) exchanger-3 (NHE3) is crucial for intestinal Na+ absorption and its reduction has been implicated in infectious and Inflammatory Bowel Diseases (IBD)-associated diarrhea. Epigenetic mechanisms such as DNA methylation are involved in the pathophysiology of IBD. Whether changes in DNA methylation are involved in modulating intestinal NHE3 gene expression is not known. Caco-2 and HUTU-80 cells were used as models of human intestinal epithelial cells (IECs). Normal C57/BL6, wild type or GADD45b KO mice were used as in vivo models. NHE3 gene DNA methylation levels were assessed by MBDCap (MethyMiner...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - November 22, 2017 Category: Physiology Authors: Kumar A, Malhotra P, Coffing HP, Priyamvada S, Natarajan Anbazhagan A, Krishnan HR, Gill RK, Alrefai WA, Gavin DP, Pandey SC, Dudeja PK, Saksena S Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Overexpression of microRNA-495 improves the intestinal mucosal barrier function by targeting STAT3 via inhibition of the JAK/STAT3 signaling pathway in a mouse model of ulcerative colitis
Publication date: Available online 12 October 2017 Source:Pathology - Research and Practice Author(s): Xian-Qun Chu, Jing Wang, Guang-Xiang Chen, Guan-Qi Zhang, De-Yong Zhang, Yong-Yan Cai We aim to investigate the role of microRNA-495 (miR-495) in the intestinal mucosal barrier by indirectly targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase-signal transducer and activator of transcription (JAK)/STAT3 signaling pathway in a mouse model of ulcerative colitis (UC). BALB/c mice were selected for establishing a mice model of UC, and intestinal tissues of normal and UC mice were coll...
Source: Pathology Research and Practice - October 13, 2017 Category: Pathology Source Type: research

Expression of Human Cathelicidin Peptide LL-37 in Inflammatory Bowel Disease.
This article is protected by copyright. All rights reserved. PMID: 28872665 [PubMed - as supplied by publisher]
Source: Clinical and Developmental Immunology - September 5, 2017 Category: Allergy & Immunology Authors: Kusaka S, Nishida A, Takahashi K, Bamba S, Yasui H, Kawahara M, Inatomi O, Sugimoto M, Andoh A Tags: Clin Exp Immunol Source Type: research

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