PubMed Central (PMC3 - NLM DTD)
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Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
American Journal of Physiology - Gastrointestinal and Liver Physiology
Mostrando recursos 121 - 140 de 731
121.
Steatohepatitis in laboratory opossums exhibiting a high lipemic response to dietary cholesterol and fat - Chan, Jeannie; Sharkey, Francis E.; Kushwaha, Rampratap S.; VandeBerg, Jane F.; VandeBerg, John L.
Plasma VLDL and LDL cholesterol were markedly elevated (>40-fold) in high-responding opossums, but moderately elevated (6-fold) in low-responding opossums after they had consumed a high-cholesterol and high-fat diet for 24 wk. In both high- and low-responding opossums, plasma triglycerides were slightly elevated, threefold and twofold, respectively. Dietary challenge also induced fatty livers in high responders, but not in low responders. We studied the lipid composition, histopathological features, and gene expression patterns of the fatty livers. Free cholesterol (2-fold), esterified cholesterol (11-fold), and triglycerides (2-fold) were higher in the livers of high responders than those in low responders, whereas free fatty...
122.
Calcium-sensing receptor inhibits secretagogue-induced electrolyte secretion by intestine via the enteric nervous system - Cheng, Sam X.
Bacterial toxins such as cholera toxin induce diarrhea by both direct epithelial cell generation of cyclic nucleotides as well as stimulation of the enteric nervous system (ENS). Agonists of the extracellular calcium-sensing receptor (CaSR) can reduce toxin-stimulated fluid secretion in ENS-absent colonic epithelial crypts by increasing phosphodiesterase-dependent cyclic-nucleotide degradation. Here we show that the CaSR is also highly expressed in tetrodotoxin (TTX)-sensitive neurons comprising the ENS, suggesting that CaSR agonists might also function through neuronal pathways. To test this hypothesis, rat colon segments containing intact ENS were isolated and mounted on Ussing chambers. Basal and cyclic nucleotide-stimulated electrolyte secretions were...
123.
Nitric oxide modifies chromatin to suppress ICAM-1 expression during colonic inflammation - Li, Qingjie; Sarna, Sushil K.
Nitric oxide (NO) is an established inflammatory mediator. However, it remains controversial whether NO enhances the inflammatory response in the colon or suppresses it. We investigated the epigenetic regulation of Icam-1 expression by NO following induction of colonic inflammation in rats by 2,4,6-trinitrobenzene sulfonic (TNBS) acid and obtaining colonic muscularis externae tissues 24 h later. TNBS inflammation induced intercellular adhesion molecule-1 (ICAM-1) expression by translocating NF-κB to the nucleus. The incubation of inflamed tissues with S-nitrosoglutathione (GSNO) did not affect the nuclear translocation of NF-κB; however, it suppressed the NF-κB binding to DNA. Chromatin immunoprecipitation analysis (ChIP)-qPCR assays showed that...
124.
Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice - Benight, Nancy M.; Stoll, Barbara; Marini, Juan C.; Burrin, Douglas G.
Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesized that orally administered MTA would be bioavailable and reduce morbidity associated with experimental colitis. We examined clinical, histological, and molecular markers of disease in mice provided oral MTA before (preventative) or after (therapy) the induction of colitis with 3% dextran sulfate sodium (DSS). We found a reduction in disease activity, weight loss, myeloperoxidase activity, and histological damage in...
125.
Gut mucosal injury in neonates is marked by macrophage infiltration in contrast to pleomorphic infiltrates in adult: evidence from an animal model - MohanKumar, Krishnan; Kaza, Niroop; Jagadeeswaran, Ramasamy; Garzon, Steven A.; Bansal, Anchal; Kurundkar, Ashish R.; Namachivayam, Kopperuncholan; Remon, Juan I.; Bandepalli, C. Rekha; Feng, Xu; Weitkamp, Joern-Hendrik; Maheshwari, Akhil
Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. In tissue samples of NEC, we identified numerous macrophages and a few neutrophils but not many lymphocytes. We hypothesized that these pathoanatomic characteristics of NEC represent a common tissue injury response of the gastrointestinal tract to a variety of insults at a specific stage of gut development. To evaluate developmental changes in mucosal inflammatory response, we used trinitrobenzene sulfonic acid (TNBS)-induced inflammation as a nonspecific insult and compared mucosal injury in newborn vs. adult mice. Enterocolitis was induced in 10-day-old pups and adult mice (n = 25 animals per...
126.
Urocortins and CRF type 2 receptor isoforms expression in the rat stomach are regulated by endotoxin: role in the modulation of delayed gastric emptying - Yuan, Pu-Qing; Wu, S. Vincent; Taché, Yvette
Peripheral activation of corticotropin-releasing factor receptor type 2 (CRF2) by urocortin 1, 2, or 3 (Ucns) exerts powerful effects on gastric function; however, little is known about their expression and regulation in the stomach. We investigated the expression of Ucns and CRF2 isoforms by RT-PCR in the gastric corpus (GC) mucosa and submucosa plus muscle (S+M) or laser captured layers in naive rats, their regulations by lipopolysaccharide (LPS, 100 μg/kg ip) over 24 h, and the effect of the CRF2 antagonist astresssin2-B (100 μg/kg sc) on LPS-induced delayed gastric emptying (GE) 2-h postinjection. Transcripts of Ucns and CRF2b, the most...
127.
Reducing endoplasmic reticulum stress does not improve steatohepatitis in mice fed a methionine- and choline-deficient diet - Henkel, Anne S.; Dewey, Amanda M.; Anderson, Kristy A.; Olivares, Shantel; Green, Richard M.
Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of nonalcoholic steatohepatitis. The ER stress response is activated in the livers of mice fed a methionine- and choline-deficient (MCD) diet, yet the role of ER stress in the pathogenesis of MCD diet-induced steatohepatitis is unknown. Using chemical chaperones on hepatic steatosis and markers of inflammation and fibrosis in mice fed a MCD diet, we aim to determine the effects of reducing ER stress. C57BL/6J mice were fed a MCD diet with or without the ER chemical chaperones 4-phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) for 2 wk. TUDCA and...
128.
Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells - Zimmerman, Mary A.; Singh, Nagendra; Martin, Pamela M.; Thangaraju, Muthusamy; Ganapathy, Vadivel; Waller, Jennifer L.; Shi, Huidong; Robertson, Keith D.; Munn, David H.; Liu, Kebin
Butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit protective effects toward inflammatory diseases such as ulcerative colitis (UC) and inflammation-mediated colorectal cancer. Recent studies have shown that chronic IFN-γ signaling plays an essential role in inflammation-mediated colorectal cancer development in vivo, whereas genome-wide association studies have linked human UC risk loci to IFNG, the gene that encodes IFN-γ. However, the molecular mechanisms underlying the butyrate-IFN-γ-colonic inflammation axis are not well defined. Here we showed that colonic mucosa from patients with UC exhibit increased signal transducer and activator of transcription 1 (STAT1) activation, and this STAT1...
129.
The role of the superior laryngeal nerve in esophageal reflexes - Lang, I. M.; Medda, B. K.; Jadcherla, S.; Shaker, R.
The aim of this study was to determine the role of the superior laryngeal nerve (SLN) in the following esophageal reflexes: esophago-upper esophageal sphincter (UES) contractile reflex (EUCR), esophago-lower esophageal sphincter (LES) relaxation reflex (ELIR), secondary peristalsis, pharyngeal swallowing, and belch. Cats (N = 43) were decerebrated and instrumented to record EMG of the cricopharyngeus, thyrohyoideus, geniohyoideus, and cricothyroideus; esophageal pressure; and motility of LES. Reflexes were activated by stimulation of the esophagus via slow balloon or rapid air distension at 1 to 16 cm distal to the UES. Slow balloon distension consistently activated EUCR and ELIR from all areas...
130.
A nomenclature for intestinal in vitro cultures - Stelzner, Matthias; Helmrath, Michael; Dunn, James C. Y.; Henning, Susan J.; Houchen, Courtney W.; Kuo, Calvin; Lynch, John; Li, Linheng; Magness, Scott T.; Martin, Martin G.; Wong, Melissa H.; Yu, Jian
Many advances have been reported in the long-term culture of intestinal mucosal cells in recent years. A significant number of publications have described new culture media, cell formations, and growth patterns. Furthermore, it is now possible to study, e.g., the capabilities of isolated stem cells or the interactions between stem cells and mesenchyme. However, at the moment there is significant variation in the way these structures are described and named. A standardized nomenclature would benefit the ability to communicate and compare findings from different laboratories using the different culture systems. To address this issue, members of the NIH Intestinal Stem...
131.
c-Jun/AP-1 is required for CCK-induced pancreatic acinar cell dedifferentiation and DNA synthesis in vitro - Guo, Lili; Sans, Maria Dolors; Hou, Yanan; Ernst, Stephen A.; Williams, John A.
Endogenous CCK plays an important role in pancreatic regeneration after pancreatitis. We used primary culture of mouse pancreatic acinar cells to evaluate the effect of CCK on acinar cell morphology and gene expression and to determine signaling pathways required for proliferation of acinar cells in vitro. Over 4 days in culture, cells grew out from acini and formed patches of monolayer, which displayed a reduced expression of acinar cell markers including digestive enzymes and Mist1 and an increased expression of ductal and embryonic markers, including cytokeratin 7, β-catenin, E-cadherin, pdx-1, and nestin. There was no appearance of stellate cell markers....
132.
Ferritin upregulates hepatic expression of bone morphogenetic protein 6 and hepcidin in mice - Feng, Qi; Migas, Mary C.; Waheed, Abdul; Britton, Robert S.; Fleming, Robert E.
Hepcidin is a hepatocellular hormone that inhibits the release of iron from certain cell populations, including enterocytes and reticuloendothelial cells. The regulation of hepcidin (HAMP) gene expression by iron status is mediated in part by the signaling molecule bone morphogenetic protein 6 (BMP6). We took advantage of the low iron status of juvenile mice to characterize the regulation of Bmp6 and Hamp1 expression by iron administered in three forms: 1) ferri-transferrin (Fe-Tf), 2) ferric ammonium citrate (FAC), and 3) liver ferritin. Each of these forms of iron enters cells by distinct mechanisms and chemical forms. Iron was parenterally administered to...
133.
Intestinal epithelial CD98 synthesis specifically modulates expression of colonic microRNAs during colitis - Charania, Moiz A.; Ayyadurai, Saravanan; Ingersoll, Sarah A.; Xiao, Bo; Viennois, Emilie; Yan, Yutao; Laroui, Hamed; Sitaraman, Shanthi V.; Merlin, Didier
The transmembrane glycoprotein CD98 is known to be involved in intestinal inflammation. In the present study, we found that CD98 overexpression in intestinal epithelial cells does not normally affect the expression of colonic (epithelial and immune cell) microRNAs (miRNAs), small noncoding RNAs that posttranscriptionally regulate a wide variety of biological processes. However, upon dextran sulfate sodium (DSS) treatment, the expression of several colonic miRNAs, but not miRNAs from other tissues such as liver and spleen, were differentially regulated in mice overexpressing CD98 in epithelial cells compared with wild-type (WT) animals. For example, the level of colonic miRNA 132 was not...
134.
Effect of peripheral administration of cholecystokinin on food intake in apolipoprotein AIV knockout mice - Yoshimichi, Go; Lo, Chunmin C.; Tamashiro, Kellie L. K.; Ma, Liyun; Lee, Dana M.; Begg, Denovan P.; Liu, Min; Sakai, Randall R.; Woods, Stephen C.; Yoshimatsu, Hironobu; Tso, Patrick
Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 μg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food...
135.
Downregulation of the CCK-B receptor in pancreatic cancer cells blocks proliferation and promotes apoptosis - Fino, Kristin K.; Matters, Gail L.; McGovern, Christopher O.; Gilius, Evan L.; Smith, Jill P.
Gastrin stimulates the growth of pancreatic cancer cells through the activation of the cholecystokinin-B receptor (CCK-BR), which has been found to be overexpressed in pancreatic cancer. In this study, we proposed that the CCK-BR drives growth of pancreatic cancer; hence, interruption of CCK-BR activity could potentially be an ideal target for cancer therapeutics. The effect of CCK-BR downregulation in the human pancreatic adenocarcinoma cells was examined by utilizing specific CCK-BR-targeted RNA interference reagents. The CCK-BR receptor expression was both transiently and stably downregulated by transfection with selective CCK-BR small-interfering RNA or short-hairpin RNA, respectively, and the effects on cell growth...
136.
Knockout of Mkp-1 exacerbates colitis in Il-10-deficient mice - Matta, Ranyia; Barnard, John A.; Wancket, Lyn M.; Yan, Jing; Xue, Jianjing; Grieves, Jessica; Frazier, W. Joshua; Nelin, Leif; Cato, Andrew C. B.; Liu, Yusen
Il-10-deficient mice develop colitis associated with exaggerated Th1/Th17 responses and are a valuable model of inflammatory bowel disease. Mkp-1 is a major negative regulator of MAPKs, and its expression is enhanced by IL-10. To understand the role of Mkp-1 in the regulation of intestinal mucosal immune responses, we studied the effect of Mkp-1 deletion on the pathogenesis of colitis in Il-10−/− mice. We found that knockout of Mkp-1 on an Il-10−/− background accelerated the development of colitis. Compared with Il-10−/− mice, colitis not only appeared earlier but also was more severe in Il-10−/−/Mkp-1−/− mice. Il-10−/− mice exhibited a mild intestinal...
137.
Activation of rat intestinal mucosal mast cells by fat absorption - Ji, Yong; Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick
Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D2 (PGD2) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections...
138.
Esophageal functional impairments in experimental eosinophilic esophagitis - Mavi, Parm; Rajavelu, Priya; Rayapudi, Madhavi; Paul, Richard J.; Mishra, Anil
Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease. Despite the increasing diagnosis of EoE globally, the causes of EoE and other esophageal eosinophilic disorders are not clearly understood. EoE pathology includes accumulation of inflammatory cells (e.g., eosinophils, mast cells), characteristic endoscopic features (e.g., furrows, the formation of fine concentric mucosal rings, exudates), and functional impairments (e.g., esophageal stricture, dysmotility). We hypothesized that the esophageal structural pathology and functional impairments of EoE develop as a consequence of the effector functions of the accumulated inflammatory cells. We analyzed eosinophils (anti-major basic protein immunostaining), esophageal stricture (X-ray barium swallowing), and esophageal motility...
139.
Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2 - Miura, Kouichi; Yang, Ling; van Rooijen, Nico; Ohnishi, Hirohide; Seki, Ekihiro
Inflammatory cell infiltration in the liver is a hallmark of nonalcoholic steatohepatitis (NASH). The chemokine-chemokine receptor interaction induces inflammatory cell recruitment. CC-chemokine receptor (CCR)2 is expressed on hepatic macrophages and hepatic stellate cells. This study aims to investigate the therapeutic potential of CCR2 to NASH. Twenty-two weeks on a choline-deficient amino acid-defined (CDAA) diet induced steatosis, inflammatory cell infiltration, and liver fibrosis with increased CCR2 and monocyte chemoattractant protein (MCP)-1 expression in the wild-type livers. The infiltrated macrophages expressed CD68, CCR2, and a marker of bone marrow-derived monocytes, Ly6C. CCR2−/− mice had less steatosis, inflammatory cell infiltration, and fibrosis, and...
140.
Genetic epidemiology and pharmacogenetics in irritable bowel syndrome - Camilleri, Michael; Katzka, David A.
The objectives of this review are twofold. Our first objective is to evaluate the evidence supporting a role for genetics in irritable bowel syndrome (IBS). Specific examples of the associations of genetic variation and symptoms, syndromes, and intermediate phenotypes, including neurotransmitter (serotonergic, α2-adrenergic, and cannabinoid) mechanisms, inflammatory pathways (IL-10, TNFα, GNβ3, and susceptibility loci involved in Crohn's disease), and bile acid metabolism, are explored. The second objective is to review pharmacogenetics in IBS, with the focus on cytochrome P-450 metabolism of drugs used in IBS, modulation of motor and sensory responses to serotonergic agents based on the 5-hydroxytryptamine (5-HT) transporter-linked...
121.
