Curcumin Inhibits T Follicular Helper Cell Differentiation in Mice with Dextran Sulfate Sodium (DSS)-Induced Colitis

2021 ◽  
pp. 1-19
Author(s):  
Hai-Yan Wang ◽  
Wei Ge ◽  
Su-Qing Liu ◽  
Jian Long ◽  
Qing-Qing Jiang ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Curcuma Longa ◽  
Colon Tissue ◽  
Change Rate ◽  
Protein Levels ◽  
Follicular Helper ◽  
Inflammatory Bowel ◽  
T Follicular Helper Cell ◽  
Pro Inflammatory Cytokines

Follicular helper T cells (Tfh) regulate the differentiation of germinal center B cells and maintain humoral immunity. Notably, imbalances in Tfh differentiation often lead to the development of autoimmune diseases, including inflammatory bowel disease (IBD). Curcumin, a natural product derived from Curcuma longa, is effective in relieving IBD in humans and animals, and its mechanisms of immune regulation need further elaboration. In this study, dextran sodium sulfate induced ulcerative colitis in BALB/c mice, and curcumin was administered simultaneously for 7 days. Curcumin effectively upregulated the change rate of mouse weight, colonic length, down-regulated colonic weight, index of colonic weight, colonic damage score and the levels of pro-inflammatory cytokines IL-6, IL-12, IL-23 and TGF-[Formula: see text]1 in colonic tissues of colitis mice. Importantly, curcumin regulated the differentiation balance of Tfh and their subpopulation in colitis mice; the percentages of Tfh (CD4[Formula: see text]CXCR5[Formula: see text]BCL-6[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-L1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]ICOS[Formula: see text], Tfh17 and Tem-Tfh were downregulated significantly, while CD4[Formula: see text]CXCR5[Formula: see text]Blimp-1[Formula: see text], Tfh1, Tfh10, Tfh21, Tfr, Tcm-Tfh and Tem-GC Tfh were upregulated. In addition, curcumin inhibited the expression of Tfh-related transcription factors BCL-6, p-STAT3, Foxp1, Roquin-1, Roquin-2 and SAP, and significantly upregulated the protein levels of Blimp-1 and STAT3 in colon tissue. In conclusion, curcumin may be effective in alleviating dextran sulfate sodium-induced colitis by regulating Tfh differentiation.

scholarly journals Curcumin Regulated the Homeostasis of Memory T Cell and Ameliorated Dextran Sulfate Sodium-Induced Experimental Colitis

2021 ◽  
Vol 11 ◽  
Author(s):  
You-Bao Zhong ◽  
Zeng-Ping Kang ◽  
Bu-Gao Zhou ◽  
Hai-Yan Wang ◽  
Jian Long ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Peripheral Blood ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Experimental Colitis ◽  
Immune Memory ◽  
Effector Memory ◽  
Colon Tissue ◽  
Inflammatory Bowel

Immune memory is protective against reinvasion by pathogens in the homeostatic state, while immune memory disorders can cause autoimmune disease, including inflammatory bowel disease. Curcumin is a natural compound shown to be effective against human inflammatory bowel disease and experimental colitis, but the underlying mechanism is unclear. Here, experimental colitis was induced by dextran sulfate sodium (DSS) in this study. Significant changes in the percentages of naïve, central memory T (TCM), and effector memory (TEM) cells and their CD4+ and CD8+ subsets were found in the peripheral blood of mice with colitis using flow cytometry. After 7 days of continuous curcumin (100 mg/kg/day) administration, the DSS-induced experimental colitis was effectively relieved, with significant decreases in the ratio of day weight to initial body weight, colonic weight, pathological injury score, levels of proinflammatory cytokines IL-7, IL-15, and IL-21, colonic mucosal ulceration, and amount of inflammatory infiltrate. Importantly, curcumin significantly restored the percentages of naïve, TCM, and TEM cells and their CD4+ and CD8+ subpopulations. In addition, curcumin significantly inhibited the activation of the JAK1/STAT5 signaling pathway, downregulation of JAK1, STAT5, and p-STAT5 proteins in colon tissue, and upregulation of PIAS1 proteins. These results suggested that curcumin effectively regulated the differentiation of naïve, TCM, and TEM cells in the peripheral blood to alleviate DSS-induced experimental colitis, which might be related to the inhibition of JAK1/STAT5 signaling activity.

scholarly journals Longitudinal Microbiome Analysis in a Dextran Sulfate Sodium-Induced Colitis Mouse Model

2021 ◽  
Vol 9 (2) ◽  
pp. 370
Author(s):  
Hyunjoon Park ◽  
Soyoung Yeo ◽  
Seokwon Kang ◽  
Chul Sung Huh
Keyword(s):  
Mouse Model ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Bleeding ◽  
Cross Sectional ◽  
Microbiome Analysis ◽  
Inflammatory Bowel ◽  
Factor Design ◽  
The Individual

The role of the gut microbiota in the pathogenesis of inflammatory bowel disease (IBD) has been in focus for decades. Although metagenomic observations in patients/animal colitis models have been attempted, the microbiome results were still indefinite and broad taxonomic presumptions were made due to the cross-sectional studies. Herein, we conducted a longitudinal microbiome analysis in a dextran sulfate sodium (DSS)-induced colitis mouse model with a two-factor design based on serial DSS dose (0, 1, 2, and 3%) and duration for 12 days, and four mice from each group were sacrificed at two-day intervals. During the colitis development, a transition of the cecal microbial diversity from the normal state to dysbiosis and dynamic changes of the populations were observed. We identified genera that significantly induced or depleted depending on DSS exposure, and confirmed the correlations of the individual taxa to the colitis severity indicated by inflammatory biomarkers (intestinal bleeding and neutrophil-derived indicators). Of note, each taxonomic population showed its own susceptibility to the changing colitis status. Our findings suggest that an understanding of the individual susceptibility to colitis conditions may contribute to identifying the role of the gut microbes in the pathogenesis of IBD.

scholarly journals Rosa canina L. Can Restore Endoplasmic Reticulum Alterations, Protein Trafficking and Membrane Integrity in a Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease Phenotype

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 441
Author(s):  
Dalanda Wanes ◽  
Mohamad Toutounji ◽  
Hichem Sebai ◽  
Sandra Rizk ◽  
Hassan Y. Naim
Keyword(s):  
Inflammatory Bowel Disease ◽  
Endoplasmic Reticulum ◽  
Lipid Rafts ◽  
Protein Trafficking ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Membrane Integrity ◽  
Membrane Glycoproteins ◽  
Rosa Canina ◽  
Inflammatory Bowel

Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins.

Sucralose enhances the susceptibility of dextran sulfate sodium (DSS) induced colitis in mice with changes in gut microbiota

2021 ◽  
Author(s):  
Mengru Guo ◽  
Xinran Liu ◽  
Yiwei Tan ◽  
Fangyuan Kang ◽  
Xinghua Zhu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Artificial Sweeteners ◽  
Epidemiological Changes ◽  
Inflammatory Bowel

Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. It’s approval and uses correlate many of the worldwide epidemiological changes of inflammatory bowel disease...

scholarly journals Resistant Maltodextrin Alleviates Dextran Sulfate Sodium-Induced Intestinal Inflammatory Injury by Increasing Butyric Acid to Inhibit Proinflammatory Cytokine Levels

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shilan Wang ◽  
Shiyi Zhang ◽  
Shimeng Huang ◽  
Zhenhua Wu ◽  
Jiaman Pang ◽  
...  
Keyword(s):  
Butyric Acid ◽  
Proinflammatory Cytokines ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Interleukin 1 ◽  
Control Group ◽  
Colon Tissue ◽  
Significant Difference ◽  
Resistant Maltodextrin

Inflammatory bowel disease (IBD), one kind of intestinal chronic inflammatory disease, is characterized by colonic epithelial barrier injury, overproduction of proinflammatory cytokines, and fewer short-chain fatty acids (SCFAs). The present study is aimed at testing the hypothesis that resistant maltodextrin (RM), a soluble dietary fiber produced by starch debranching, alleviated dextran sulfate sodium- (DSS-) induced colitis in mice. Female C57BL/6 mice with or without oral administration of 50 mg/kg RM for 19 days were challenged with 3% DSS in drinking water to induce colitis (from day 14 to day 19). Although RM could not reverse DSS-induced weight loss or colon shortening, it reduced inflammatory cell infiltration and epithelial damage in colon tissue, as well as the transfer of intestinal permeability indicators including serum diamine oxidase (DAO) and D-lactic acid (D-LA). ELISA analysis indicated that RM significantly suppressed the increase of Th1 cytokines induced by DSS in the colon such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The levels of proinflammatory cytokines interleukin-1β (IL-1β), IL-17, and IL-8 in the DSS group were significantly higher than those in the control group and RM group, but no significant difference was observed in the RM-DSS group compared with the RM group. Interestingly, IL-10 levels of the DSS group were significantly higher than those of the other groups. With respect to SCFAs, DSS administration significantly decreased the concentration of faecal butyric acid while the RM-DSS group showed a tendency to increase (P=0.08). In general, RM alleviated dextran sulfate sodium-induced intestinal inflammation through increasing the level of butyric acid and subsequently inhibiting the expression of proinflammatory cytokines.

Dietary intake of Lycium ruthenicum Murray ethanol extract inhibits colonic inflammation in dextran sulfate sodium-induced murine experimental colitis

2020 ◽  
Vol 11 (4) ◽  
pp. 2924-2937
Author(s):  
Shuai Zong ◽  
Liu Yang ◽  
Hyun Jin Park ◽  
Jinglei Li
Keyword(s):  
Inflammatory Cell ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Barrier ◽  
Ethanol Extract ◽  
Experimental Colitis ◽  
Lycium Ruthenicum ◽  
Intestinal Barrier Integrity ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Lycium ruthenicum Murray extract protected experimental colitis by inhibiting pro-inflammatory cytokines production, inflammatory cell infiltration, inflammatory mediators activation and oxidative stress, and restored intestinal barrier integrity.

The role of the complement and contact systems in the dextran sulfate sodium-induced colitis model: the effect of C1 inhibitor in inflammatory bowel disease

2010 ◽  
Vol 298 (6) ◽  
pp. G878-G883 ◽  
Author(s):  
Fengxin Lu ◽  
Stacey M. Fernandes ◽  
Alvin E. Davis
Keyword(s):  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Complement C3 ◽  
C1 Inhibitor ◽  
Inflammatory Bowel

The complement and contact systems may be involved in the pathophysiological process of inflammatory bowel disease (IBD). C1 inhibitor (C1INH) is the most important inhibitor of both the complement and contact systems. We evaluated the role of these systems and the effect of both active and inactive forms of C1INH (iC1INH) in dextran sulfate sodium (DSS)-induced colitis mouse model. Three percent DSS was used in drinking water to induce colitis in complement C3-deficient (C3−/−) mice, bradykinin type 2 receptor deficient (Bk2R−/−) mice, and C57BL/6 mice. After ten days DSS exposure, C3−/− mice exhibited markedly less weight loss than wild-type (WT) mice (12 ± 3.3% vs. 30 ± 1.2%, P < 0.05) and developed a milder disease-activity index (DAI), histological score, colon shortening, and myeloperoxidase (MPO) elevation ( P < 0.05, respectively). The Bk2R−/− mice were not protected from the disease. Seven-day treatment with either native C1INH or iC1INH reduced the severity of the disease in WT mice, as indicated by decreased weight loss (15 ± 1.8%, 14 ± 2.1% vs. 30 ± 1.2%, P < 0.05, respectively), DAI, intestinal tissue damage, and MPO elevation compared with untreated WT DSS control mice ( P < 0.05, respectively). These findings suggest that complement plays a role in the development of DSS-induced colitis and that blockade of the complement system might be useful for the acute phase of IBD treatment. C1INH, however, leads to an amelioration of DSS-induced colitis via a mechanism that does not involve the inhibition of complement or contact system activation but does result in significant suppression of leukocyte infiltration.

scholarly journals Portulaca Extract Attenuates Development of Dextran Sulfate Sodium Induced Colitis in Mice through Activation of PPARγ

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Rui Kong ◽  
Hui Luo ◽  
Nan Wang ◽  
Jingjing Li ◽  
Shizan Xu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Peroxisome Proliferator ◽  
Potential Candidate ◽  
Inflammatory Bowel ◽  
Peroxisome Proliferator Activated Receptors ◽  
Induced Apoptosis ◽  
Inflammatory Effect

Portulaca oleracea L. is a traditional Chinese medicine, which has been used as adjuvant therapy for inflammatory bowel disease (IBD). However, the mechanism of its activity in IBD still remains unclear. Since previous studies have documented the anti-inflammatory effect of peroxisome proliferator activated receptors-γ (PPAR-γ), Portulaca regulation of PPAR-γ in inflammation was examined in current study. Ulcerative colitis (UC) was generated by 5% dextran sulfate sodium (DSS) in mice and four groups were established as normal control, DSS alone, DSS plus mesalamine, and DSS plus Portulaca. Severity of UC was evaluated by body weight, stool blood form, and length of colorectum. Inflammation was examined by determination of inflammatory cytokines (TNF-a, IL-6, and IL-1a). Portulaca extract was able to attenuate development of UC in DSS model similar to the treatment of mesalazine. Moreover, Portulaca extract inhibited proinflammatory cytokines release and reduced the level of DSS-induced NF-κB phosphorylation. Furthermore, Portulaca extract restored PPAR-γ level, which was reduced by DSS. In addition, Portulaca extract protected DSS induced apoptosis in mice. In conclusion, Portulaca extract can alleviate colitis in mice through regulation of inflammatory reaction, apoptosis, and PPAR-γ level; therefore, Portulaca extract can be a potential candidate for the treatment of IBD.

scholarly journals Dextran sulfate sodium mouse model of inflammatory bowel disease evaluated for systemic genotoxicity via blood micronucleus and Pig-a gene mutation assays

Mutagenesis ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 161-167
Author(s):  
Christopher Kirby ◽  
Ayesha Baig ◽  
Svetlana L Avlasevich ◽  
Dorothea K Torous ◽  
Shuchang Tian ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Model ◽  
Bowel Disease ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
High Dose ◽  
Significant Treatment ◽  
Blood Samples ◽  
Inflammatory Bowel ◽  
Blood Specimens

Abstract Inflammatory bowel disease (IBD) is an important risk factor for gastrointestinal cancers. Inflammation and other carcinogenesis-related effects at distal, tissue-specific sites require further study. In order to better understand if systemic genotoxicity is associated with IBD, we exposed mice to dextran sulfate sodium salt (DSS) and measured the incidence of micronucleated cells (MN) and Pig-a mutant phenotype cells in blood erythrocyte populations. In one study, 8-week-old male CD-1 mice were exposed to 0, 1, 2, 3 or 4% w/v DSS in drinking water. The 4-week in-life period was divided into four 1-week intervals—alternately on then off DSS treatment. Low volume blood samples were collected for MN analysis at the end of each week, and cardiac blood samples were collected at the end of the 4-week period for Pig-a analyses. The two highest doses of DSS were observed to induce significant increases in reticulocyte frequencies. Even so, no statistically significant treatment-related effects on the genotoxicity biomarkers were evident. While one high-dose mouse showed modestly elevated MN frequencies during the DSS treatment cycles, it also exhibited exceptionally high reticulocyte frequencies (e.g. 18.7% at the end of the second DSS cycle). In a second study, mice were treated with 0 or 4% DSS for 9–18 consecutive days. Exposure was continued until rectal bleeding or morbidity was evident, at which point the treatment was terminated and blood was collected for MN analysis. The Pig-a assay was conducted on samples collected 29 days after the start of treatment. The initial blood specimens showed highly elevated reticulocyte frequencies in DSS-exposed mice (mean ± SEM = 1.75 ± 0.10% vs. 13.04 ± 3.66% for 0 vs. 4% mice, respectively). Statistical analyses showed no treatment-related effect on MN or Pig-a mutant frequencies. Even so, the incidence of MN versus reticulocytes in the DSS-exposed mice were positively correlated (linear fit R2 = 0.657, P = 0.0044). Collectively, these results suggest that in the case of the DSS CD-1 mouse model, systemic effects include stress erythropoiesis but not remarkable genotoxicity. To the extent MN may have been slightly elevated in a minority of individual mice, these effects appear to be secondary, likely attributable to stimulated erythropoiesis.

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