Pilot study: duodenal MDR1 and COX2 gene expression in cats with inflammatory bowel disease and low-grade alimentary lymphoma

Objectives Multidrug resistance 1 (MDR1) encodes a protein called P-glycoprotein (P-gp), which serves as an efflux pump membrane protein implicated in intestinal homeostasis and drug resistance. Cyclooxygenase-2 (COX2) is a key enzyme in the synthesis of proinflammatory prostaglandins, tumourigenesis and in mucosal defence. Despite the importance of MDR1 and COX2, changes in their mRNA levels have not been studied in cats with inflammatory bowel disease (IBD) and low-grade alimentary lymphoma (LGAL). The present study aimed to determine the mRNA levels of MDR1 and COX2 in cats with IBD and LGAL, and to evaluate their correlation with clinical signs, histological severity and between genes. Methods Cats diagnosed with IBD (n = 20) and LGAL (n = 9) between 2008 and 2015 were included in the current study. Three healthy animals composed the healthy control cats group in which endoscopy was performed immediately before the ovariohysterectomy. All duodenal biopsy samples were obtained by endoscopy. Feline chronic enteropathy activity index was calculated for all cases. IBD histopathology was classified according to severity. MDR1 and COX2 mRNA levels were determined by absolute reverse transcriptase-quantitative real-time PCR. Results Statistically significant differences were observed for MDR1 and COX2 mRNA levels between the IBD and LGAL groups. No correlations were observed between molecular gene expression, feline chronic enteropathy activity index and histological grading for IBD, and between MDR1 and COX2 genes. However, a positive statistically significant correlation was observed between MDR1 and COX2 expression in the duodenum of cats. Conclusions and relevance MDR1 and COX2 gene expression is increased in cats with LGAL compared with cats with IBD. The control group tended to have lower values than both diseased groups. These results suggest that these genes may be involved in the pathogenesis of IBD or LGAL in cats.

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Differential Expression of IL-36 Family Members and IL-38 by Immune and Nonimmune Cells in Patients with Active Inflammatory Bowel Disease

BioMed Research International ◽

10.1155/2018/5140691 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 17

Author(s):

Gabriela Fonseca-Camarillo ◽

Janette Furuzawa-Carballeda ◽

Emilio Iturriaga-Goyon ◽

Jesús K. Yamamoto-Furusho

Keyword(s):

Gene Expression ◽

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Family Members ◽

Control Group ◽

Clinical Activity ◽

Gut Inflammation ◽

Active Inflammatory Bowel Disease ◽

Inflammatory Bowel

IL-1 family includes IL-38 (IL-1F10) and the subfamily of IL-36 and is the central mediators of inflammatory diseases, including pustular psoriasis, atopic dermatitis, rheumatoid arthritis, and gut inflammation. The purpose of the study was to evaluate on tissue of the patients with inflammatory bowel disease (IBD), the IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 gene and cell expression and its correlation with clinical activity. Patients and Methods. A cross-sectional and comparative study was performed. Seventy patients with IBD and 30 noninflamed non-IBD controls were enrolled. Gene expression was measured by RT-PCR. Protein expression was detected by double-staining immunohistochemistry. Results. The mRNA expression of IL-36 family members but not IL-38 was increased in colonic mucosa from patients with active ulcerative colitis versus Crohn’s disease group and noninflammatory control group (P<0.05). However, only gene expression of IL-38 was increased in tissue from patients with inactive ulcerative colitis versus active disease and control group (P<0.005). Conversely, gene expression of IL-36Ra was significantly higher in colonic tissue from patients with active versus inactive ulcerative colitis and noninflamed control group (P<0.05). A differential protein overexpression of IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 by intestinal epithelial cells, macrophages, CD8+ T cells, and/or versus dendritic cells (pDCs) was found in patients with active inflammatory bowel disease compared with noninflamed controls. Conclusion. IL-38 and IL-36 family members’ expression was increased by immune and nonimmune cells in patients with active inflammatory bowel disease. These cytokines and IL-36Ra might represent novel therapeutic targets in patients with gut inflammation.

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Clinical Signs, Activity Indices and Prognostic Indicators in Dogs with Idiopathic Inflammatory Bowel Disease

Indian Journal of Animal Research ◽

10.18805/ijar.b-4399 ◽

2021 ◽

Author(s):

M. Sandhya Bhavani ◽

S. Kavitha ◽

S. Vairamuthu ◽

K. Vijayarani ◽

Abid Ali Bhat

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Serum Alkaline Phosphatase ◽

Activity Index ◽

Clinical Signs ◽

Prognostic Indicators ◽

Histologic Evidence ◽

Inflammatory Bowel ◽

Idiopathic Inflammatory Bowel Disease

Background: Canine inflammatory bowel disease (IBD) includes a set of diseases characterized by the presence of recurrent gastrointestinal clinical signs and histologic evidence of intestinal inflammation. Diagnosis can only be made by excluding other possible causes of enteritis. Since the diagnosis of this disease is of great challenge to the veterinarians and currently very little work have been carried out in India, the present study was planned and conducted to study the clinicopathological changes and prognostic indicators of idiopathic inflammatory bowel disease (IBD) in dogs.Methods: After a detailed clinical, laboratoty and endoscopic examination, 33 IBD dogs with signs of chronic gastrointestinal disorders and histologic evidence of mucosal lymphocytic plasmacytic infiltration were selected for the study.Result: Moderate to severe form of IBD with haematochezia as a chief complaint was predominantly recorded. Haematobiochemical changes were not remarkable except a rise in serum alkaline phosphatase level. Decreased IgA expression was observed in serum by flowcytometry indicating impaired mucosal immunity in IBD dogs. It was observed that, increased clinical inflammatory bowel disease activity index score (CIBDAI), increased C-Reactive Protein, decreased cobalamin and folate may act as negative predictors in idiopathic IBD.

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Probiotics alleviate inflammatory bowel disease in mice by regulating intestinal microorganisms-bile acid-NLRP3 inflammasome pathway

Acta Biochimica Polonica ◽

10.18388/abp.2020_5597 ◽

2021 ◽

Author(s):

Zongshi Liu ◽

Hong Wang

Keyword(s):

Inflammatory Bowel Disease ◽

Bile Acid ◽

Bowel Disease ◽

Nlrp3 Inflammasome ◽

Control Group ◽

Mrna Levels ◽

Probiotic Group ◽

Intestinal Microorganisms ◽

Probiotic Treatment ◽

Inflammatory Bowel

The objective of the present study was to elucidate the mechanism of intestinal microorganisms- bile acid- NLRP3 inflammasome regulation in mice with inflammatory bowel disease treated with probiotics. The abnormal activation of NLRP3 inflammasome is the main pathogenic factor that leads to the development of chronic colitis in IL-10–/– mice. In this study, we divided the IL-10–/– and wild-type mice on a C57BL/6 background into 3 groups: control group (wt mice, n=10), IBD group (IL-10–/– mice, n=10), and probiotic group (IL-10–/– mice treated with probiotics, n=10). The analyses included mRNA levels of cytokines and protein expression of NLRP3 inflammasome and NOD2, as well as colorimetric determination of Wnt, Notch and BMP activity in colon tissue and fresh colon mass. The fresh colon mass was increased in the IBD mice when compared with the control and the probiotic groups (P<0.05). The histological score of the proximal colon in the IBD group was higher than in two other groups (P<0.05). The probiotic group showed lower levels of IFN-γ, IL-17F, IL-1α and IL-25 mRNA compared to the IBD group (P<0.05). The main components of NLRP3 inflammasome (NLRP3, ASC, caspase-1 and IL-1β) and NOD2 were increased in IBD group compared to the control, and decreased after probiotic treatment (P<0.05). FXR, TGR5, vitamin D, and CAR were all increased in IBD group compared to the control and probiotic groups (P<0.05). In conclusion, probiotics modulated the intestinal microbial-bile acid-NLRP3 inflammation in IBD mice.

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Is Oxidative Stress Associated with Activation and Pathogenesis of Inflammatory Bowel Disease?

Journal of Medical Biochemistry ◽

10.1515/jomb-2017-0013 ◽

2017 ◽

Vol 36 (4) ◽

pp. 341-348 ◽

Cited By ~ 7

Author(s):

Mahmut Yuksel ◽

Ihsan Ates ◽

Mustafa Kaplan ◽

Mehmet Fettah Arikan ◽

Yasemin Ozderin Ozin ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Bowel Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Colorimetric Method ◽

Control Group ◽

Strong Positive Correlation ◽

Positive Correlation ◽

Inflammatory Bowel

SummaryBackground: We aimed to determine the levels of total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) and paraoxonase1/arylesterase levels in inflammatory bowel disease (IBD), and the relation be - tween these molecules and the activity index of the disease. Methods: Eighty IBD patients (ulcerative colitis (UC)/Crohn disease (CD) 40/40) and 80 control group participants were included in the study. Oxidative stress parameters were measured using the colorimetric method. As disease activity indexes, the endoscopic activity index (EAI) was used for UC and the CD activity index (CDAI) was used for CD. Results: In IBD patients, mean TAS (1.3±0.2 vs 1.9±0.2, respectively; p<0.001) and arylesterase (963.9±232.2 vs 1252.9±275, respectively; p<0.001) levels were found to be lower and TOS level (5.6±1.6 vs 4.0±1.0, respectively; p<0.001) and OSI rate (4.5±1.6 vs 2.2±0.8, respectively; p<0.001) were found to be higher compared to the control group. A strong positive correlation was found between EAI and TOS levels (r=0.948, p<0.001) and OSI rate (r=0.894, p<0.001) for UC patients. A very strong positive correlation was found between EAI and TOS levels (r=0.964, p<0.001) and OSI rate (r=0.917, p<0.001) for CD patients. It was found in a stepwise regression model that C-reactive protein, OSI and arylesterase risk factors were predictors of IBD compared to the control group. Conclusion: Increased oxidative stress level in IBD patients and the detection of OSI rate as an independent predictor for disease activity indexes lead to the idea that oxidative stress might be related to the pathogenesis of IBD.

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Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease

Digestive Diseases and Sciences ◽

10.1007/bf01537105 ◽

1989 ◽

Vol 34 (10) ◽

pp. 1528-1535 ◽

Cited By ~ 29

Author(s):

Linda C. Duffy ◽

Maria A. Zielezny ◽

Marie Riepenhoff-Talty ◽

Tim E. Byers ◽

James Marshall ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Vasoactive Intestinal Peptide ◽

Bowel Disease ◽

Activity Index ◽

Clinical Activity ◽

Inflammatory Bowel

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37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0037 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A38-A38

Author(s):

Shilpa Ravindran ◽

Heba Sidahmed ◽

Harshitha Manjunath ◽

Rebecca Mathew ◽

Tanwir Habib ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Mesenchymal Transition ◽

Increased Risk ◽

Hamad Medical Corporation ◽

Inflammatory Bowel ◽

Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

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Dental and periodontal disease in patients with inflammatory bowel disease

Clinical Oral Investigations ◽

10.1007/s00784-021-03835-6 ◽

2021 ◽

Author(s):

Christopher X. W. Tan ◽

Henk S. Brand ◽

Bilgin Kalender ◽

Nanne K. H. De Boer ◽

Tymour Forouzanfar ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Periodontal Disease ◽

Bowel Disease ◽

Health Problems ◽

Control Group ◽

Age And Gender ◽

Preventive Dental Care ◽

Dmft Index ◽

Inflammatory Bowel ◽

And Gender

Abstract Objectives Although bowel symptoms are often predominant, inflammatory bowel disease (IBD) patients can have several oral manifestations. The aim of this study was to investigate the prevalence of dental caries and periodontal disease in patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to an age and gender-matched control group of patients without IBD. Material and methods The DMFT (Decayed, Missing, Filled Teeth) scores and the DPSI (Dutch Periodontal Screening Index) of 229 IBD patients were retrieved from the electronic health record patient database axiUm at the Academic Centre for Dentistry Amsterdam (ACTA) and were compared to the DMFT scores and DPSI from age and gender-matched non-IBD patients from the same database. Results The total DMFT index was significantly higher in the IBD group compared to the control group. When CD and UC were analyzed separately, a statistically significant increased DMFT index was observed in CD patients but not in UC patients. The DPSI did not differ significantly between the IBD and non-IBD groups for each of the sextants. However, in every sextant, IBD patients were more frequently edentulous compared to the control patients. Conclusion CD patients have significantly more dental health problems compared to a control group. Periodontal disease did not differ significantly between IBD and non-IBD groups as determined by the DPSI. Clinical relevance It is important that IBD patients and physicians are instructed about the correlation between their disease and oral health problems. Strict oral hygiene and preventive dental care such as more frequent checkups should be emphasized by dental clinicians.

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