scholarly journals P025 Evaluation of endoplasmic reticulum stress in intestinal mucosa from patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S143-S144
Author(s):  
B Rodrigues ◽  
L B Pascoal ◽  
A Coope ◽  
M L S Ayrizono ◽  
M G Camargo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Er Stress ◽  
Inflammatory Cytokines ◽  
Intestinal Mucosa ◽  
Inflammatory Process ◽  
Explant Culture ◽  
Control Group ◽  
Significant Difference

Abstract Background The endoplasmic reticulum (ER) is responsible for the synthesis and processing of secretory and membrane proteins. In some cases, proteins cannot reach their final conformation and they remain unfolded in the ER lumen. The accumulation of unfolded proteins leads to a state of stress in the ER (ER stress) that is considered toxic to the cells. As a result, cells may respond by driving the proteins to degradation, pausing the transcription process, or even inducing apoptosis.1 ER stress has recently been linked to the exacerbation of the inflammatory process in the pathogenesis of Crohn’s disease (CD).2 Therefore, our aim was to evaluate the effect of a chemical inhibitor on the activation of ER stress pathways and its modulation of pro-inflammatory cytokines. Methods After approval of a local Ethics Committee, biopsies of intestinal mucosa were collected by colonoscopy from patients with CD (CD group) and from patients without inflammatory bowel diseases (control group). Explant culture was performed to evaluate the occurrence of ER stress and was treated with a chemical ER stress inhibitor. Non-parametric tests were performed for statistical analysis adopting p < 0.05 as significant value. Results Samples were collected from 10 patients with active CD (CDEIS ≥5) and six control patients. After cell culture, a significant difference was observed in the activation of the main ER stress pathway in the CD group when compared with control group. After treatment with a chemical inhibitor, there was significant decrease in the expression of genes responsible for the activation of ER stress. In addition, a decrease in the expression of inflammatory cytokines was observed after treatment. Conclusion The use of a chemical inhibitor has been shown to be effective in significantly decreasing the activation of ER stress and to modulate the inflammation in CD. The activation of the main ER stress pathways may contribute to the inflammatory process in CD, and its blockade suggests a potential new target in the treatment of CD. References

Clinical Correlates of Urolithiasis in Ankylosing Spondylitis

2011 ◽  
Vol 38 (9) ◽  
pp. 1953-1956 ◽  
Author(s):  
NAI LEE LUI ◽  
ADELE CARTY ◽  
NIGIL HAROON ◽  
HUA SHEN ◽  
RICHARD J. COOK ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Ankylosing Spondylitis ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Functional Disability ◽  
Spinal Mobility ◽  
Joint Involvement ◽  
Control Group ◽  
Significant Difference ◽  
History Of

Objective.To determine the association between urolithiasis and syndesmophyte formation and the effect of urolithiasis on ankylosing spondylitis (AS) disease activity.Methods.In a longitudinal cohort of 504 patients with AS, we conducted an analysis of all patients with AS who have a history of urolithiasis. All patients met the modified New York criteria for AS. Demographics, clinical characteristics, extraarticular features, and comorbidities are systematically recorded in the database. We compared disease activity, functional indices, medical therapy and radiographic damage between AS patients with (Uro+) and without urolithiasis (Uro–) using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).Results.Thirty-eight patients with AS (7.5%) had a history of urolithiasis in our cohort. Seventy-six patients with AS who did not have urolithiasis, matched for age, sex, and ethnicity, were selected as controls. Patients who were Uro+ were more likely to have more functional disability, based on the Bath AS Functional Index (BASFI; mean 5.3 vs 3.6 in control group, p = 0.003). Trends were noted in the Uro+ group toward higher Bath AS Disease Activity Index (BASDAI; mean 4.9 vs 4.0, p = 0.09), more peripheral joint involvement (p = 0.075), and higher frequency of biologic therapy (p = 0.09). No significant difference was detected in mSASSS or the Bath AS Metrology Index (BASMI). Significant association with diabetes mellitus (DM; p = 0.016) and Crohn’s disease (p = 0.006) was noted in the Uro+ group.Conclusion.Although there is no acceleration of syndesmophyte formation or spinal mobility restriction, more functional disability was detected in the urolithiasis group. The higher risk with concomitant DM or Crohn’s disease should alert clinicians to these comorbidities in Uro+ patients with AS.

scholarly journals Endoplasmic Reticulum Stress in Subepithelial Myofibroblasts Increases the TGF-β1 Activity That Regulates Fibrosis in Crohn’s Disease

2020 ◽  
Vol 26 (6) ◽  
pp. 809-819 ◽  
Author(s):  
Chao Li ◽  
John R Grider ◽  
Karnam S Murthy ◽  
Jaime Bohl ◽  
Emily Rivet ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Direct Interaction ◽  
Binding Activity ◽  
Luciferase Reporter ◽  
Stress Components ◽  
Tgf Β1

Abstract Background Endoplasmic reticulum (ER) stress is an essential response of epithelial and immune cells to inflammation in Crohn’s disease. The presence and mechanisms that might regulate the ER stress response in subepithelial myofibroblasts (SEMFs) and its role in the development of fibrosis in patients with Crohn’s disease have not been examined. Methods Subepithelial myofibroblasts were isolated from the affected ileum and normal ileum of patients with each Montreal phenotype of Crohn’s disease and from normal ileum in non-Crohn’s subjects. Binding of GRP78 to latent TGF-β1 and its subcellular trafficking was examined using proximity ligation-hybridization assay (PLA). The effects of XBP1 and ATF6 on TGF-β1 expression were measured using DNA-ChIP and luciferase reporter assay. Endoplasmic reticulum stress components, TGF-β1, and collagen levels were analyzed in SEMF transfected with siRNA-mediated knockdown of DNMT1 and GRP78 or with DNMT1 inhibitor 5-Azacytidine or with overexpression of miR-199a-5p. Results In SEMF of strictured ileum from patients with B2 Crohn’s disease, expression of ER stress sensors increased significantly. Tunicamycin elicited time-dependent increase in GRP78 protein levels, direct interaction with latent TGF-β1, and activated TGF-β1 signaling. The TGFB1 DNA-binding activity of ATF-6α and XBP1 were significantly increased and elicited increased TGFB1 transcription in SEMF-isolated from affected ileum. The levels of ER stress components, TGF-β1, and collagen expression in SEMF were significantly decreased following knockdown of DNMT1 or GRP78 by 5-Azacytidine treatment or overexpression of miR-199a-5p. Conclusions Endoplasmic reticulum stress is present in SEMF of patients susceptible to fibrostenotic Crohn’s disease and can contribute to development of fibrosis. Targeting ER stress may represent a novel therapeutic target to prevent fibrosis in patients with fibrostenotic Crohn’s disease.

scholarly journals ER stress activation in the intestinal mucosa but not in mesenteric adipose tissue is associated with inflammation in Crohn’s disease patients

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0223105 ◽  
Author(s):  
Andressa Coope ◽  
Lívia Bitencourt Pascoal ◽  
José Diego Botezelli ◽  
Francesca Aparecida Ramos da Silva ◽  
Maria de Lourdes Setsuko Ayrizono ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Er Stress ◽  
Intestinal Mucosa ◽  
Mesenteric Adipose Tissue ◽  
Stress Activation

Evaluation of the Pro-Inflammatory ER Stress Activation in Intestinal Mucosa and Mesenteric Adipose Tissue in Crohn's Disease Patients

2017 ◽  
Vol 152 (5) ◽  
pp. S763
Author(s):  
Andressa Coope ◽  
José Diego Botezelli ◽  
Lívia A. Pascoal ◽  
Francesca R. Silva ◽  
Maria de Lourdes S. Ayrizono ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Er Stress ◽  
Intestinal Mucosa ◽  
Mesenteric Adipose Tissue ◽  
Stress Activation

scholarly journals The Prevalence of Headache in Crohn’s Disease: Single-Center Experience

2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Ulker Anadol Kelleci ◽  
Turan Calhan ◽  
Abdurrahman Sahin ◽  
Resul Kahraman ◽  
Kamil Ozdil ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
International Headache Society ◽  
Tension Type Headache ◽  
Control Group ◽  
Disease Group ◽  
Single Center Experience ◽  
Group 12 ◽  
Significant Difference ◽  
Type Headache

Objectives. This study is aimed at studying the prevalence and characteristics of different types of headaches in patients with Crohn’s disease.Materials and Methods. 51 patients in Crohn’s disease group (F/M: 26/25) and 51 patients in control group (F/M: 27/24) were involved. Patients in Crohn’s disease group were diagnosed and monitored according to European Crohn’s and Colitis Organization diagnostic criteria. The control group composed of healthy subjects with similar age and sex to Crohn’s disease group. Headache was classified using the International Headache Society II criteria.Results. Headache was reported by 35/51 (68.6%) patients in Crohn’s disease group and 21/51 (41.2%) patients in the control group. The prevalence of headache was statistically high in the group with Crohn’s disease (OR: 3.125 (95% CI: 1.38–7.04);p=0.01). Comparing two groups with respect to their subtypes of headaches resulted in that the tension-type headache was statistically (p=0.008) higher in Crohn’s disease group (26/51) than in the control group (12/51). However, no significant difference was found in the migraine-type headache (p=1).Conclusions. This study indicates that the prevalence of headache is high in patients with Crohn’s disease and most commonly associated with the tension-type headache.

scholarly journals Moxibustion and Acupuncture Ameliorate Crohn’s Disease by Regulating the Balance between Th17 and Treg Cells in the Intestinal Mucosa

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chen Zhao ◽  
Chunhui Bao ◽  
Jing Li ◽  
Yifang Zhu ◽  
Siyao Wang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Molecular Markers ◽  
Treatment Group ◽  
Crohn's Disease ◽  
Intestinal Mucosa ◽  
Immune Cell ◽  
Treg Cells ◽  
Control Group ◽  
Therapeutic Effects ◽  
Immune Cell Subsets

Previous studies have demonstrated that acupuncture is beneficial to patients with Crohn’s disease (CD), but the mechanism underlying its therapeutic effects remains unclear. To identify the mechanism by which acupuncture treats CD, the balance between Th17 and Treg cells was assessed in CD patients. In this study, Ninety-two CD patients were randomly and equally assigned to a treatment group that were treated with herb-partitioned moxibustion and acupuncture or a control group with wheat bran-partitioned moxibustion and superficial acupuncture. The effect of these treatments on Th17 and Treg cells and their related molecular markers in the intestinal mucosa were detected before (week 0) and after (week 12) treatment. The results suggested that the ratio of Th17 and Treg cells was significantly decreased after treatment and that the levels of IL-17 and RORγt in the intestinal mucosa were obviously reduced, while the expression of FOXP3 was increased after treatment in both groups. In the treatment group, the expression of these molecules was more markedly regulated than the control group. In conclusion, moxibustion and acupuncture have been shown to regulate the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restore the balance between these immune cell subsets.

P141 GREEN TEA POLYPHENOL EPIGALLOCATECHIN-3-GALLATE DIFFERENTIALLY MODULATES ENDOPLASMIC RETICULUM STRESS-MEDIATED WOUND HEALING PROCESS IN SUBEPITHELIAL MYOFIBROBLASTS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S35-S35
Author(s):  
Chao Li ◽  
John Kuemmerle
Keyword(s):  
Wound Healing ◽  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Er Stress ◽  
Healing Process ◽  
Wound Healing Process ◽  
Er Stress Response ◽  
Tnbs Colitis ◽  
Tgf Β1

Abstract Epigallocatechin-3-gallate (EGCG) has multifaceted roles in the preclinical treatment of diseases including liver and lung fibrosis. EGCG has also been tested with fewer reported side effects than therapeutic drugs. Previously we showed that increase in endoplasmic reticulum (ER) stress response in subepithelial myofibroblasts (SEMF) contributes to activation of TGF-β1 and resultant intestinal fibrosis in patients with fibrostenotic Crohn’s disease. Moreover, different migratory potential of myofibroblasts isolated from inflamed, fibrostenotic, or fistulized Crohn’s disease mucosa could be an explanation for impaired or excess wound healing and subsequently for fistula or fibrosis in patients with Crohn’s disease. To investigate the effect of EGCG on ER stress-mediated wound healing process, SEMF were isolated from normal ileum and affected ileum in the same patient with Crohn’s disease. Cells were cultured and treated with EGCG (10 μg/ml), AG1024 (a tyrosine kinase inhibitor, 6 μM), U1026 (an ERK inhibitor, 6 μM), LY294002 (a PI3K inhibitor, 10 μM), SB202190 (a p38 inhibitor, 50 nM), 4-PBA (a chemical chaperone, 10 μg/ml), and MG132 (a NF-KB inhibitor, 3 μM) for 2 hours in serum free medium. Cell lysates were obtained for Western blot analysis. An ER stress agonist tunicamycin (5 μg/ml) was incubated with SEMF for different time points. Wound healing assay was used in a cell monolayer, capturing the images at the beginning and at regular intervals during cell migration to close the wound, and comparing the images to quantify the migratory potential of the cells. In vivo effect of EGCG was tested in a murine TNBS colitis model and observed by Storz Coloview standard operating procedures. Here we showed that EGCG further decreased endogenous GRP78 protein expression by 18∼29±1.5% in SEMF compared to that treated with different inhibitors targeting other non-ER stress signals. EGCG prevented tunicamycin-induced migratory potential of SEMF isolated from normal ileum by 40±2.5%, 65±3.3% after 48 and 72 hours, as well as cell proliferation by 85±3.3%, 120±6.1% after 48 and 72 hours, respectively. Moreover, EGCG also further decreased cell migratory potential of SEMF isolated from affected ileum by 15±1.2% and 50±1.8% compared to the control group after 48 and 72 hours, respectively. Coloview showed that EGCG decreased inflammatory activity in the mice colon compared to TNBS colitis group after 8-week treatment. Ongoing study includes methylene blue staining of the colonic mucosa during endoscopy, endoscopic scoring of inflammation activity, and trichrome staining of collagen production in a colonic biopsy. Taken together, EGCG alleviates ER Stress response, leads to greater inhibition of migratory potential of SEMF, and decreases TGF-β1 and collagen productions, which is the major molecular feature of fibrosis.

scholarly journals P081 Resolvin D2 attenuates colonic inflammation of Crohn’s disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S182-S182
Author(s):  
L B Pascoal ◽  
B B Palma ◽  
F H Chaim ◽  
G Nogueira ◽  
B L Rodrigues ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Mucosa ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Lipid Mediators ◽  
Control Group ◽  
Inflammatory Disorder ◽  
Tertiary Referral Hospital ◽  
Colonic Inflammation

Abstract Background Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Usually, the clinical management are based on sulphasalazine, corticosteroid, immunomodulators, biologics therapy and bioactive small molecules. However, new therapeutic strategies involving the inflammatory process are being proposed as the use of pro-resolution lipid mediators. This study aimed to investigate the potential therapeutical role of Resolvin D2 (RvD2) in the intestinal mucosa of CD patients and its therapeutic potential. Methods The study included 16 CD patients, 8 patients in remission (CDR) and 8 with active disease (CDA) and 6 healthy subjects in the control group (CTR); all were followed up in tertiary referral hospital. Blood sample and colonic biopsies were collected during colonoscopy. Disease activity was determined by the Crohn’s Disease Endoscopic Index of Severity (CDEIS). The serum blood level of RvD2 was determined by enzymatic immunosorption assay (ELISA). Intestinal biopsies were submitted to cell culture and treated with Infliximab (IFX) or RvD2. The expression of inflammatory cytokines was evaluated by real-time PCR and RvD2 levels through the ELISA. A nonparametric test was used for statistical analysis, with adopted p<0.05. The study was approved by the University of Campinas research ethics committee. Results The intestinal mucosa of the CDA group showed higher levels of pro-inflammatory markers, such as, IL1β (p=0.008 and p=0.01), IL6 (p=0.002), IL23 (p=0.03) and S100A8 (p=0.004 and p=0.01), compared to CTR and CDR groups, respectively. Although serum RvD2 levels of CDA (p=0.002) and CDR (p=0.004) groups were increased when compared to the CTR group, there is no differences between CDA and CDR groups (p>0.05). However, intestinal explants of the CDA group treated with RvD2 showed a significantly decrease of IL1β expression (p<0.05) when compared to the non-treated biopsies in the ex vivo culture experiments, similar to what was as verified by IFX treatment (p<0.05). Conclusion The results suggest the participation of RvD2 in the modulation of colonic inflammation associated with CD. RvD2 showed to be as effective as IFX in attenuating the pro-inflammatory response present in the intestinal mucosa of patients with CD and provide insights into pro-resolution lipid mediators approaches to modulate chronic inflammation.

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