Downregulation of CPI-17 contributes to dysfunctional motility in chronic intestinal inflammation model mice and ulcerative colitis patients

SummaryBackground: Reactive oxygen species can attack and damage almost every molecule found in living cells, including proteins, carbohydrates, lipids, and DNA. For this reason, their production is normally tightly controlled. Among the most important defenses against these radicals are the super oxide dismutase (SOD) enzymes and catalase (CAT). In creasing attention has been given to the role of reactive oxygen metabolites in the pathogenesis of ulcerative colitis (UC), which is defined as an idiopathic and chronic intestinal inflammation. Accordingly, we hypothesized a relation between genetic polymorphisms in the two antioxidant enzymes SOD1 A251G (rs2070424) and CAT C-262T (rs1001179) and the risk of UC.Methods: The present case-control study included 109 UC patients (46 males and 50 females) and 186 (67 males and 119 females) gender-matched healthy controls. Genotyping was done by the PCR-RFLP method.Results: After adjusting for age and gender, a significant association was observed between the AG+GG genotypes of SOD1 A251G polymorphism (vs. AA genotype) and risk of UC (OR=0.29, 95% CI: 0.10-0.86, P= 0.025) after adjusting for age and gender. Our statistical analysis revealed that the CAT C-262T polymorphism did not associate with the risk of UC before and/or after adjusting for age and gender.Conclusions: Based on the present statistical analysis, the G allele of the SOD1 A251G polymorphism decreases the risk of UC, thus it might be assumed that the G allele has a protective role.

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Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽

10.3390/cells8060517 ◽

2019 ◽

Vol 8 (6) ◽

pp. 517 ◽

Cited By ~ 12

Author(s):

Claudia Burrello ◽

Maria Rita Giuffrè ◽

Angeli Dominique Macandog ◽

Angelica Diaz-Basabe ◽

Fulvia Milena Cribiù ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Immune Cells ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Experimental Colitis ◽

Fecal Microbiota ◽

Microbiota Composition ◽

Chronic Intestinal Inflammation ◽

Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

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High-Fat Diet Promotes DSS-Induced Ulcerative Colitis by Downregulated FXR Expression through the TGFB Pathway

BioMed Research International ◽

10.1155/2020/3516128 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Di Zhao ◽

Chenwen Cai ◽

Qiyi Chen ◽

Shuang Jin ◽

Bo Yang ◽

...

Keyword(s):

Ulcerative Colitis ◽

High Fat Diet ◽

Target Genes ◽

Intestinal Inflammation ◽

Farnesoid X Receptor ◽

Mucosal Barrier ◽

High Fat ◽

Colon Rectal Cancer ◽

Chronic Intestinal Inflammation

Ulcerative colitis is one of the IBD which cause a chronic intestinal inflammation and dysfunctional of the mucosal barrier. For now, the incident of UC was steadily increased all over the world. It has become a novel independent risk factor of several severe diseases especially colon-rectal cancer. However, the etiology of UC was still obscure. Previous studies show that high-fat diet contributed to the pathogenesis of immune system dysregulation, and farnesoid X receptor (FXR) was also implicated in the pathogenesis of various inflammatory symptoms. Yet, their inner roles in the pathogenesis of UC have not been mentioned. In this study, we aim to investigate the role of FXR in UC. High-fat diet (HFD) promotes the progression of DSS-induced UC, shows an increasing secretion of bile acid in serum, and leads to a downregulation of FXR target genes (FXRα, Shp, and lbabp). Adding FXR agonist FexD rescues the phenotype induced by high-fat diet, whereas TGFBRI inhibitor SB431542 abrogates the restoration by FexD in DSS-induced UC mice. To further verify the relationship between the FXR and TGFB signaling pathway, we made a UC-HFD model in the Caco2 cell line. Results shows the same conclusion that FXR mitigate UC inflammation through a TGFB-dependent pathway. These results expand the role of FXR in ulcerative colitis and suggest that FXR activation may be considered a therapeutic strategy for UC.

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VEGF, basic-FGF, and TGF-β in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(00)02320-0 ◽

2001 ◽

Vol 96 (3) ◽

pp. 822-828 ◽

Cited By ~ 3

Author(s):

S Kanazawa

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Inflammation ◽

Basic Fgf ◽

Chronic Intestinal Inflammation

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The Role of Cytokines in Inflammatory Bowel Disease

Mediators of Inflammation ◽

10.1155/s0962935194000013 ◽

1994 ◽

Vol 3 (1) ◽

pp. 3-9 ◽

Cited By ~ 2

Author(s):

G. Radford-Smith ◽

D. P. Jewell

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Intestinal Inflammation ◽

Inflammatory Lesions ◽

Immunoregulatory Cytokines ◽

Current Thinking ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation ◽

Th1 And Th2

Cytokines play an important role in the development and persistence of the inflammatory lesions seen in Crohn's disease and ulcerative colitis. This review discusses the current thinking of the role of cytokines in chronic intestinal inflammation including the involvement of immunoregulatory cytokines within the Th1 and Th2 subsets.

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VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation

The American Journal of Gastroenterology ◽

10.1111/j.1572-0241.2001.03527.x ◽

2001 ◽

Vol 96 (3) ◽

pp. 822-828 ◽

Cited By ~ 16

Author(s):

Shigeo Kanazawa ◽

Tsukasa Tsunoda ◽

Eishi Onuma ◽

Toshimitsu Majima ◽

Mitsuyasu Kagiyama ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Inflammation ◽

Tgf Beta ◽

Basic Fgf ◽

Chronic Intestinal Inflammation

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Quercetin Exposure Suppresses the Inflammatory Pathway in Intestinal Organoids from Winnie Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20225771 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5771 ◽

Cited By ~ 7

Author(s):

Manuela Dicarlo ◽

Gabriella Teti ◽

Giulio Verna ◽

Marina Liso ◽

Elisabetta Cavalcanti ◽

...

Keyword(s):

Ulcerative Colitis ◽

Intestinal Inflammation ◽

Experimental System ◽

Wild Type ◽

Intestinal Organoids ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Small Intestinal ◽

Chronic Intestinal Inflammation

Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses.

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Ulcerative Colitis associated with Sclerosing Cholangitis and Autoimmune Hepatitis

Acta Medica Marisiensis ◽

10.2478/amma-2013-0028 ◽

2013 ◽

Vol 59 (2) ◽

pp. 115-120

Author(s):

Andrei Hoduț ◽

I Simedrea ◽

I Sabău ◽

Oana Belei ◽

Ionela Babi

Keyword(s):

Ulcerative Colitis ◽

Autoimmune Hepatitis ◽

Sclerosing Cholangitis ◽

Intestinal Inflammation ◽

Overlap Syndrome ◽

Extraintestinal Manifestations ◽

Aminosalicylic Acid ◽

Diagnostic Features ◽

Chronic Intestinal Inflammation ◽

Bloody Stools

AbstractIntroduction: Ulcerative colitis is a chronic intestinal inflammation, part of inflammatory bowel disease, which also includes Crohn’s disease. Both have extraintestinal manifestations, but those that tend to occur more commonly with ulcerative colitis include chronic active hepatitis, pyoderma gangrenosum and ankylosing spondylitis. Many individuals present with overlapping non-diagnostic features of more than one of these conditions that is referred to in the literature as autoimmune overlap syndrome. Sclerosing cholangitis associated with IBD is often referred to as overlap syndrome.Material and methods: We present the case of a 15-year-old female, with an association between ulcerative colitis, primitive sclerosing cholalangitis and autoimmune hepatitis. She was admitted for: diarrheic bloody stools, abdominal pain, diminished appetite, headache and aphthous stomatitis. Blood sample analysis revealed: hypochromic anemia, iron deficiency, high levels of transaminase, abnormal protein electrophoresis, positive anti-neutrophil cytoplasmic antibodies and anti-smooth muscle antibodies, high level of faecal calprotectin, modified biliary tract on imaging of digestive system and suggestive modifications of colic mucosa for ulcerative colitis. We administered treatment with Arginine Chloride 5%, Sorbitol 10%, Aspartic acid, Vitamin B6, Ursodeoxycholic acid, 5-aminosalicylic acid.Results: With the administered therapy the evolution was good, macroscopic blood disappeared from stools, and tests for blood trace in stool were also negative.Conclusions: The patient had simultaneous onset of diarrhea with bloody stools and extraintestinal manifestations. Immunological markers didn’t fully match any of the associated diseases, so we concluded that there was an overlap syndrome. Budesonide was effective on both hepatic and intestinal disease.

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