Unique Regulation of Coupled NaCl Absorption by Inducible Nitric Oxide in a Spontaneous SAMP1/YitFc Mouse Model of Chronic Intestinal Inflammation

2021 ◽  
Author(s):  
Subha Arthur ◽  
Balasubramanian Palaniappan ◽  
Sheuli Afroz ◽  
Uma Sundaram
Keyword(s):  
Nitric Oxide ◽  
Intestinal Inflammation ◽  
Common Symptom ◽  
Experimental Conditions ◽  
Nacl Absorption ◽  
Samp1 Mouse ◽  
Inflammatory Bowel ◽  
And Control ◽  
Chronic Intestinal Inflammation ◽  
Inducible Nitric Oxide

Abstract In the small intestine, Na:H (NHE3) and Cl:HCO3 (DRA or PAT1) exchangers present in the brush border membrane (BBM) of absorptive villus cells are primarily responsible for the coupled absorption of NaCl, the malabsorption of which causes diarrhea, a common symptom of inflammatory bowel disease (IBD). Inducible nitric oxide (iNO), a known mediator of inflammation, is increased in the mucosa of the chronically inflamed IBD intestine. An SAMP1/YitFc (SAMP1) mouse, a spontaneous model of chronic ileitis very similar to human IBD, was used to study alterations in NaCl absorption. The SAMP1 and control AKR mice were treated with I-N(6)-(1-Iminoethyl)-lysine (L-NIL) to inhibit iNO production, and DRA/PAT1 and NHE3 activities and protein expression were studied. Though Na:H exchange activity was unaffected, Cl:HCO3 activity was significantly decreased in SAMP1 mice due to a reduction in its affinity for Cl, which was reversed by L-NIL treatment. Though DRA and PAT1 expressions were unchanged in all experimental conditions, phosphorylation studies indicated that DRA, not PAT1, is affected in SAMP1. Moreover, the altered phosphorylation levels of DRA was restored by L-NIL treatment. Inducible NO mediates the inhibition of coupled NaCl absorption by decreasing Cl:HCO3 but not Na:H exchange. Specifically, Cl:HCO3 exchanger DRA but not PAT1 is regulated at the level of its phosphorylation by iNO in the chronically inflamed intestine.

scholarly journals Inducible Nitric Oxide Regulates Na-Glucose Co-Transport in a Spontaneous SAMP1/YitFc Mouse Model of Chronic Ileitis

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3116
Author(s):  
Balasubramanian Palaniappan ◽  
Shanmuga Sundaram ◽  
Subha Arthur ◽  
Sheuli Afroz ◽  
Uma Sundaram
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Bowel Disease ◽  
Small Intestine ◽  
Mouse Model ◽  
Brush Border Membrane ◽  
Common Symptom ◽  
Samp1 Mouse ◽  
Inflammatory Bowel ◽  
Akr Mice ◽  
Inducible Nitric Oxide

In mammalian small intestine, glucose is primarily absorbed via Na-dependent glucose co-transporter (SGLT1) on the brush border membrane (BBM) of absorptive villus cells. Malabsorption of nutrients (e.g., glucose) leads to malnutrition, a common symptom of inflammatory bowel disease (IBD), where the mucosa is characterized by chronic inflammation. Inducible nitric oxide (iNO) is known to be elevated in IBD mucosa. SAMP1/YitFc (SAMP1) mouse is a spontaneous model of chronic ileitis that develops lesions in its terminal ileum, very similar to human IBD. How SGLT1 may be affected in SAMP1 model of chronic ileitis is unknown. Ten-week-old SAMP1 mice with AKR mice as control were treated with N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) to inhibit iNO production. Intracellular NO levels were found to be increased in villus cells from SAMP1 mice. Moreover, SGLT1 and Na+/K+-ATPase activities and BBM SGLT1 expression were significantly decreased. However, L-NIL treatment reduced the intracellular iNO production, and reversed both downregulated SGLT1 and Na+/K+-ATPase activities in SAMP1 mice. Inhibition of iNO by L-NIL treatment also significantly reversed the BBM SGLT1 protein expression in SAMP1 mice. L-NIL reversed the inflammation mediated downregulation of SGLT1 activity by restoring the BBM SGLT1 expression. Thus, regulation of SGLT1 in chronic ileitis is likely mediated by iNO.

scholarly journals Inducible Nitric Oxide Regulates Brush Border Membrane Na-Glucose Co-transport, but Not Na:H Exchange via p38 MAP Kinase in Intestinal Epithelial Cells

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 111 ◽  
Author(s):  
Palanikumar Manoharan ◽  
Shanmuga Sundaram ◽  
Soudamani Singh ◽  
Uma Sundaram
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Mechanism Of Inhibition ◽  
Chronic Intestinal Inflammation ◽  
Inducible Nitric Oxide

During chronic intestinal inflammation in rabbit intestinal villus cells brush border membrane (BBM) Na-glucose co-transport (SGLT1), but not Na/H exchange (NHE3) is inhibited. The mechanism of inhibition is secondary to a decrease in the number of BBM co-transporters. In the chronic enteritis mucosa, inducible nitric oxide (iNO) and superoxide production are known to be increased and together they produce abundant peroxynitrite (OONO), a potent oxidant. However, whether OONO mediates the SGLT1 and NHE3 changes in intestinal epithelial cells during chronic intestinal inflammation is unknown. Thus, we determined the effect of OONO on SGLT1 and NHE3 in small intestinal epithelial cell (IEC-18) monolayers grown on trans well plates. In cells treated with 100 μM SIN-1 (OONO donor) for 24 h, SGLT1 was inhibited while NHE3 activity was unaltered. SIN-1 treated cells produced 40 times more OONO fluorescence compared to control cells. Uric acid (1mM) a natural scavenger of OONO prevented the OONO mediated SGLT1 inhibition. Na+/K+-ATPase which maintains the favorable trans-cellular Na gradient for Na-dependent absorptive processes was decreased by OONO. Kinetics studies demonstrated that the mechanism of inhibition of SGLT1 by OONO was secondary to reduction in the number of co-transporters (Vmax) without an alteration in the affinity. Western blot analysis showed a significant decrease in SGLT1 protein expression. Further, p38 mitogen-activated protein (MAP) kinase pathway appeared to mediate the OONO inhibition of SGLT1. Finally, at the level of the co-transporter, 3-Nitrotyrosine formation appears to be the mechanism of inhibition of SGLT1. In conclusion, peroxynitrite inhibited BBM SGLT1, but not NHE3 in intestinal epithelial cells. These changes and the mechanism of SGLT1 inhibition by OONO in IEC-18 cells is identical to that seen in villus cells during chronic enteritis. Thus, these data indicate that peroxynitrite, known to be elevated in the mucosa, may mediate the inhibition of villus cell BBM SGLT1 in vivo in the chronically inflamed intestine.

scholarly journals P315 Short-chain fatty acid profile in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S311-S312
Author(s):  
L Oliveira ◽  
L Yukie Sassaki ◽  
A Elisa Valencise Quagli ◽  
J Ribeiro de Barros
Keyword(s):  
Fatty Acid ◽  
Intestinal Inflammation ◽  
Nutrient Deficiency ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Bacterial Degradation ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
And Control ◽  
Chronic Intestinal Inflammation

Abstract Background Short-chain fatty acids (SCFAs) are products of colonic bacterial degradation of dietary fibre. They are important in the colon, affecting the morphology and function of colonocytes. SCFAs consist of a molecule with one to six carbons, of which acetate, propionate and butyrate are the most abundant. In recent decades, it has become apparent that SCFAs can play a key role in the prevention and treatment of metabolic syndrome, intestinal disorders and certain cancers. Crohn’s disease (CD) and ulcerative colitis (UC) are characterised by recurrent chronic intestinal inflammation, probably due to an inadequate immune response coupled with intestinal microbiota imbalance. The aim of this study was to evaluate the profile of SCFA in patients with UC and CD, and compared with non-ill individuals. Methods The individuals were divided into three groups: RCU, CD and control, the faeces were donated by them, and the SCFAs were measured by chromatographic analysis using a Thermo Scientific GC-MS coupled to a Thermo ISQ 230ST mass detector. All results are expressed as mean ± SEM. Results It was possible to observe a different SCFAs profile between individuals with CD and UC and control where acetate and propionate levels in patients with UC and CD were higher than in non-sick individuals and butyrate with lower levels in individuals with CD and RCU (Graph 1). SCFAs have anti-inflammatory capabilities and also a preferred energy source for colon epithelial cells, as well as lowering the pH of the colon and inhibiting the growth of pathogenic organisms. Dysbiosis decreases butyrate concentrations, which may result in nutrient deficiency at the epithelial level, altering immune responses, as well as acting directly as an anti-inflammatory agent by disabling the NFκB pathway, with a consequent decrease in inflammatory cytokine synthesis. Conclusion Thus, the reported results have implications for various physiological and pathological conditions in inflammatory bowel diseases, especially with respect to butyrate and the production of inflammatory mediators, and partly explain the beneficial effects attributed to this fatty acid in the treatment of inflammatory and inflammatory diseases support the realisation of new studies aimed at the development of therapeutic alternatives to the use of conventional anti-inflammatory drugs.

Vascular Hyporesponsiveness in Aortic Rings from Cirrhotic Rats: Role of Nitric Oxide and Endothelium

1996 ◽  
Vol 91 (6) ◽  
pp. 733-738 ◽  
Author(s):  
M. Clara Oriíz ◽  
Lourdes A. Fortepiani ◽  
Concha Martínez ◽  
Noemí M. Atucha ◽  
Joaquín García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Methyl Ester ◽  
Nitric Oxide Synthesis ◽  
Experimental Conditions ◽  
Nitric Oxide Release ◽  
Oxide Synthase ◽  
And Control ◽  
Inducible Nitric Oxide

1. The role of nitric oxide as mediator of the vascular alterations present in different models of experimental liver cirrhosis is controversial. In the present study, we evaluated the role of nitric oxide and that of the endothelium in the response to phenylephrine and acetylcholine of isolated aortic rings from chronic bile duct-ligated (29 days) rats and their corresponding controls. Experiments were performed in rings with or without endothelium, in rings pretreated with N-ω-nitro-l-arginine methyl ester (10−4 mol/l) to inhibit nitric oxide synthesis and in rings pretreated with aminoguanidine (10−4 mol/l) to inhibit inducible nitric oxide synthesis. 2. Under basal conditions, the maximum absolute tension developed in response to cumulative addition of phenylephrine was significantly decreased in rings from bile duct-ligated animals (1.62 ± 0.06 g) compared with the control rings (2.15 ± 0.099). This hyporesponsiveness to phenylephrine of rings from bile duct-ligated animals was corrected after treatment with N-ω-nitro-l-arginine methyl ester and reduced, but not completely eliminated, in rings without endothelium. In contrast, aminoguanidine did not modify the lower response to phenylephrine rings from bile duct-ligated animals. ED50 values were not different between groups under any experimental conditions. 3. The endothelium-dependent vasodilatation to acetylcholine in phenylephrine-constricted rings was similar in both groups of animals, control and bile duct ligated, under all experimental conditions. N-ω-nitro-l-arginine methyl ester pretreatment and removal of the endothelium completely abolished the response to acetylcholine in cirrhotic and control rings. 4. These results demonstrate that in aortic rings from cirrhotic, bile duct-ligated rats, increased production of nitric oxide, mainly of endothelial origin, is responsible for the lower contractile response to phenylephrine. Our data, however, do not support the involvement of the inducible nitric oxide synthase isoform in this alteration. In contrast, endothelial vasodilatory response to acetylcholine is not altered in this model of cirrhosis, which indicates that not all mechanisms of nitric oxide release are abnormal.

scholarly journals Anthocyanins and intestinal barrier function: a review

2019 ◽  
Vol 5 ◽  
pp. 18-30 ◽  
Author(s):  
Jonathan C. Valdez ◽  
Bradley W. Bolling
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Berry Anthocyanins ◽  
Chronic Intestinal Inflammation

Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation. Berries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and preventing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocyanins and their known microbial catabolites modulate intestinal barrier function.

Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Giorgos Bamias ◽  
Theresa T Pizarro ◽  
Fabio Cominelli
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Large Scale ◽  
Intestinal Inflammation ◽  
Temporal Association ◽  
Stricture Formation ◽  
Intestinal Fibrosis ◽  
Matrix Deposition ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Abstract Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.

NF-κB Activation and iNOS Expression in the Synovial Membrane of Rat Temporomandibular Joints after Induced Synovitis

2003 ◽  
Vol 82 (3) ◽  
pp. 183-188 ◽  
Author(s):  
T. Yamaza ◽  
K.F. Masuda ◽  
Y. Tsukiyama ◽  
K. Nishijima ◽  
R. Murakami ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Transcription Factors ◽  
Inos Expression ◽  
Synovial Lining ◽  
Temporomandibular Joints ◽  
Synovial Lining Cells ◽  
Oxide Synthase ◽  
And Control ◽  
Southwestern Histochemistry ◽  
Inducible Nitric Oxide

NF-κB plays a pivotal role in pathogenesis in general arthritis. However, the participation of NF-κB in inflammation of the temporomandibular joint (TMJ) is poorly understood. We examined NF-κB expression in rat TMJs with synovitis induced by condyle hypermobility. By immunohistochemistry, NF-κB immunoreactivity was found mainly in the cytoplasm, not the nucleus, of the synovial lining cells of induced-synovitis and control TMJs. Southwestern histochemistry, a new method for detecting transcription factors, showed greater NF-κB expression in the nucleus of the synovial lining cells in the hypertrophic synovium than in control synovium. Increased numbers of the synovial lining cells with immunoreactivity for inducible nitric oxide synthase (iNOS), which is transcriptionally regulated by NF-κB, were also seen in the inflamed synovium. These findings indicate that excess mechanical stress increases NF-κB activation in the TMJ and suggest that active NF-κB is involved in the progression of TMJ inflammation.

Potential of Plant-sourced Phenols for Inflammatory Bowel Disease

2019 ◽  
Vol 25 (38) ◽  
pp. 5191-5217 ◽  
Author(s):  
Hai-tao Xiao ◽  
Bo Wen ◽  
Xiang-chun Shen ◽  
Zhao-xiang Bian
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Term Treatment ◽  
Term Therapy ◽  
Inflammatory Status ◽  
Long Term Treatment ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics. In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota. In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help further development of new preventive/adjuvant regimens for IBD.

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