Local administration of 4-Thiouridine, a novel molecule with potent anti-inflammatory properties, protects against experimental colitis and arthritis

2020 ◽  
Vol 85 ◽  
pp. 106598
Author(s):  
Manish Kumar Jeengar ◽  
Sudeep Chenna Narendra ◽  
Dinesh Thummuri ◽  
Mattias Magnusson ◽  
V.G.M. Naidu ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Local Administration ◽  
Anti Inflammatory

HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway

2021 ◽  
Author(s):  
Yong Fu ◽  
Gailing Ma ◽  
Yuqian Zhang ◽  
Wenli Wang ◽  
Tongguo Shi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Camp Response Element Binding ◽  
Cellular Level ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Colitis ◽  
Anti Inflammatory

Abstract Background Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that plays a pivotal role in maintaining mucosal immune homeostasis. As a novel synthetic inhibitor of salt-inducible kinases (SIKs), HG-9-91-01 can effectively enhance IL-10 secretion at the cellular level, but its in vivo immunoregulatory effects remain unclear. In this study, we investigated the effects and underlying mechanism of HG-9-91-01 in murine colitis models. Methods The anti-inflammatory effects of HG-9-91-01 were evaluated on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium–induced colitis mice, and IL-10 knockout chronic colitis mice. The in vivo effector cell of HG-9-91-01 was identified by fluorescence-activated cell sorting and quantitative real-time polymerase chain reaction. The underlying mechanism of HG-9-91-01 was investigated via overexpressing SIKs in ANA-1 macrophages and TNBS colitis mice. Results Treatment with HG-9-91-01 showed favorable anticolitis effects in both TNBS- and DSS-treated mice through significantly promoting IL-10 expression in colonic macrophages but failed to protect against IL-10 KO murine colitis. Further study indicated that HG-9-91-01 markedly enhanced the nuclear level of cAMP response element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3), whereas treatment with lentiviruses encoding SIK protein markedly decreased the nuclear CRTC3 level in HG-9-91-01–treated ANA-1 macrophages. In addition, intracolonic administration with lentiviruses encoding SIK protein significantly decreased the nuclear CRTC3 level in the lamina propria mononuclear cells and ended the anti-inflammatory activities of HG-9-91-01. Conclusions We found that HG-9-91-01 promoted the IL-10 expression of colonic macrophages and exhibited its anticolitis activity through the SIK/CRTC3 axis, and thus it may represent a promising strategy for inflammatory bowel disease therapy.

scholarly journals Effect of a Milk-Based Fruit Beverage Enriched with Plant Sterols and/or Galactooligosaccharides in a Murine Chronic Colitis Model

Foods ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 114 ◽  
Author(s):  
Gabriel López-García ◽  
Antonio Cilla ◽  
Reyes Barberá ◽  
Amparo Alegría ◽  
María Recio
Keyword(s):  
Ulcerative Colitis ◽  
Experimental Colitis ◽  
Plant Sterols ◽  
Mice Model ◽  
Colon Tissue ◽  
Clinical Model ◽  
Need To Evaluate ◽  
Anti Inflammatory ◽  
Enriched Milk ◽  
Inflammatory Effect

The potential anti-inflammatory effect of plant sterols (PS) enriched milk-based fruit beverages (PS, 1 g/100 mL) (MfB) with/without galactooligosaccharides (GOS, 2 g/100 mL) (MfB-G) in an experimental mice model of chronic ulcerative colitis was evaluated. Beverages were orally administered to mice every day by gavage to achieve PS and GOS doses of 35 and 90 mg/kg, respectively, and experimental colitis was induced by giving mice drinking water ad libitum containing 2% (w/v) dextran sulphate sodium (DSS) for 7 days, alternating with periods without DSS up to the end of the study (56 days). MfB beverage showed significant reduction of symptoms associated to ulcerative colitis and improved the colon shortening and mucosal colonic damage, but it was not able to reduce the increase of myeloperoxidase levels produced by DSS. MfB-G showed higher incidence of bloody feces and loss of stool consistency than MfB, as well as high levels of immune cells infiltration in colon tissue and myeloperoxidase. Therefore, PS-enriched milk-based fruit beverage could be an interesting healthy food to extend the remission periods of the diseases and the need to evaluate, in a pre-clinical model, the anti-inflammatory effect of the combination of bioactive compounds in the context of a whole food matrix.

The Immunomodulatory Properties of Propyl-Propane Thiosulfonate Contribute to its Intestinal Anti-Inflammatory Effect in Experimental Colitis

2019 ◽  
Vol 63 (5) ◽  
pp. 1800653 ◽  
Author(s):  
Teresa Vezza ◽  
Francesca Algieri ◽  
José Garrido-Mesa ◽  
María Pilar Utrilla ◽  
María Elena Rodríguez-Cabezas ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity

2020 ◽  
Vol 9 (9) ◽  
pp. 2913
Author(s):  
Ji Yeon Kang ◽  
Mi-Kyung Oh ◽  
Hansol Joo ◽  
Hyun Sung Park ◽  
Dong-Hoon Chae ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Experimental Colitis ◽  
Wharton’S Jelly ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Wharton's Jelly ◽  
Indoleamine 2,3 Dioxygenase ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory

The therapeutic applications of mesenchymal stem cells (MSCs) have been actively explored due to their broad anti-inflammatory and immunomodulatory properties. However, the use of xenogeneic components, including fetal bovine serum (FBS), in the expansion media might pose a risk of xenoimmunization and zoonotic transmission to post-transplanted patients. Here, we extensively compared the physiological functions of human Wharton’s jelly-derived MSCs (WJ-MSCs) in a xeno-free medium (XF-MSCs) and a medium containing 10% FBS (10%-MSCs). Both groups showed similar proliferation potential; however, the 10%-MSCs showed prolonged expression of CD146, with higher colony-forming unit-fibroblast (CFU-F) ability than the XF-MSCs. The XF-MSCs showed enhanced adipogenic differentiation potential and sufficient hematopoietic stem cell (HSC) niche activity, with elevated niche-related markers including CXCL12. Furthermore, we demonstrated that the XF-MSCs had a significantly higher suppressive effect on human peripheral blood-derived T cell proliferation, Th1 and Th17 differentiation, as well as naïve macrophage polarization toward an M1 phenotype. Among the anti-inflammatory molecules, the production of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase 2 (NOS2) was profoundly increased, whereas cyclooxygenase-2 (COX-2) was decreased in the XF-MSCs. Finally, the XF-MSCs had an enhanced therapeutic effect against mouse experimental colitis. These findings indicate that xeno-free culture conditions improved the immunomodulatory properties of WJ-MSCs and ex vivo-expanded XF-MSCs might be an effective strategy for preventing the progression of colitis.

P151 DISRUPTION OF ENDOGENOUS ITACONATE PRODUCTION EXACERBATES EXPERIMENTAL COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S5-S6
Author(s):  
Ryan Frieler ◽  
Thomas Vigil ◽  
Richard Mortensen ◽  
Yatrik Shah
Keyword(s):  
Gene Expression ◽  
Immune Cell ◽  
Tricarboxylic Acid Cycle ◽  
Myeloid Cells ◽  
Experimental Colitis ◽  
Cell Types ◽  
Cell Phenotype ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Anti Inflammatory

Abstract Background Inflammation is a hallmark of inflammatory bowel disease and alterations in tricarboxylic acid cycle (TCA) metabolism have been identified as major regulators of immune cell phenotype during inflammation and hypoxia. The TCA cycle metabolite, itaconate, is produced by the enzyme aconitate decarboxylase 1 (Acod1) and is highly upregulated during classical macrophage activation and during experimental colitis. Itaconate and cell permeable derivatives have robust anti-inflammatory effects on macrophages, therefore we hypothesized that Acod1-produced itaconate has a protective, anti-inflammatory effect during experimental colitis. Methods and Results Wild type (WT) control and Acod1-/- mice were administered 3% Dextran Sulfate Sodium (DSS) in water for 7 days to induce experimental colitis. After DSS was discontinued, Acod1-/- mice had significantly reduced body weight recovery with increased macroscopic disease severity, and upon dissection had decreased colon length and more severe inflammation. To determine if myeloid cells are the critical Acod1/itaconate-producing cell types, we generated myeloid-specific Acod1 deficient mice, however no differences in weight loss, colon length or inflammatory gene expression were detected compared to WT controls. To test whether supplementation with exogenous itaconate could ameliorate colitis, WT mice were treated with the cell-permeable form of itaconate, dimethyl itaconate (DMI). Administration of DMI significantly improved recovery after 7 days of DSS treatment and significantly reduced inflammatory gene expression in the colon. Conclusion Our data suggest that Acod1-produced itaconate has an important role in the regulation of inflammation during experimental colitis. Although myeloid cells have been thought to be major producers of Acod1 and itaconate, our data indicate that other cell types are involved. These results highlight the importance of this immunometabolic pathway and suggest that preservation or enhancement of this pathway with natural metabolites or metabolite derivatives could have beneficial effects during colitis.

scholarly journals Anti-Inflammatory and Chemopreventive Effects of Bryophyllum pinnatum (Lamarck) Leaf Extract in Experimental Colitis Models in Rodents

2020 ◽  
Vol 11 ◽  
Author(s):  
Anderson Wilbur Lopes Andrade ◽  
Gerlane Coelho Bernardo Guerra ◽  
Daline Fernandes de Souza Araújo ◽  
Raimundo Fernandes de Araújo Júnior ◽  
Aurigena Antunes de Araújo ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Experimental Colitis ◽  
Anti Inflammatory ◽  
Bryophyllum Pinnatum

scholarly journals Anticolitic Effect of Berberine in Rat Experimental Model: Impact of PGE2/p38 MAPK Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Li Jia ◽  
Kuijin Xue ◽  
Junheng Liu ◽  
Ola A. Habotta ◽  
Lianhai Hu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
P38 Mapk ◽  
Experimental Colitis ◽  
Mucosal Damage ◽  
Isoquinoline Alkaloid ◽  
Protective Mechanism ◽  
Colon Mucosa ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
High Doses

Berberine (BER), a natural isoquinoline alkaloid, has been demonstrated to have appreciable anticolitis effects. Nevertheless, the protective mechanism of BER in ulcerative colitis (UC) is barely understood. The present study was aimed at exploring the therapeutic efficacy of BER on UC in experimental colitis rat model. Rats were orally administered with BER for seven days at low and high doses (25 and 50 mg/kg/day) before AcOH intracolonic instillation. BER significantly retrieved colon inflammation and mucosal damage indicated by inhibition of macroscopic score and lessened the levels of inflammatory biomarkers (IL-1β, IL-6, TNF-α, MPO, and PGE2). Notable downregulation of mRNA expression of p38 MAPK and increased protein expression of TGF-β were achieved by BER treatment. The anti-inflammatory potential of BER was supported by the histopathological screening of colon mucosa. In addition, BER restored colonic antioxidant capacity through elevation of GSH level and antioxidant enzymatic activities (SOD, CAT, GPx, and GR) together with reductions of both MDA and NO levels. Marked downregulation of Nos2 mRNA expression is accompanied by increased Nrf2 and Hmox-1 expressions in colon specimens treated by BER. Furthermore, BER exhibited noticeable antiapoptotic activities through decreasing proapoptotic proteins (Bax and caspase-3) and lessening antiapoptotic Bcl-2 protein in the colon mucosa. Based on these findings, BER may improve colitis markedly which may be mediated by its striking antioxidant, anti-inflammatory, and antiapoptotic properties.

Expression and secretion of lipocortin 1 in gut inflammation are not regulated by pituitary-adrenal axis

1997 ◽  
Vol 273 (2) ◽  
pp. R623-R629 ◽  
Author(s):  
N. Vergnolle ◽  
C. Comera ◽  
J. More ◽  
M. Alvinerie ◽  
L. Bueno
Keyword(s):  
Culture Medium ◽  
Experimental Colitis ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Gut Inflammation ◽  
Adrenal Axis ◽  
Histological Damage ◽  
Anti Inflammatory ◽  
Pituitary Adrenal Axis

Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.

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