scholarly journals The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C)-priming through promoting the expression of indoleamine 2,3-dioxygenase.

2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  
Keyword(s):  
Weight Loss ◽  
Disease Activity ◽  
Stromal Cells ◽  
Therapeutic Efficacy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Poly I:C ◽  
Colon Tissue ◽  
Ifn Γ

Abstract Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9.Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC.Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.

scholarly journals The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C) priming through promoting the expression of indoleamine 2,3-dioxygenase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  
Keyword(s):  
Weight Loss ◽  
Disease Activity ◽  
Stromal Cells ◽  
Therapeutic Efficacy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Poly I:C ◽  
Colon Tissue ◽  
Ifn Γ

Abstract Background Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSCs) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 upregulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.

scholarly journals The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C)-priming through promoting the expression of indoleamine 2,3-dioxygenase.

2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  
Keyword(s):  
Weight Loss ◽  
Disease Activity ◽  
Stromal Cells ◽  
Therapeutic Efficacy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Poly I:C ◽  
Colon Tissue ◽  
Ifn Γ

Abstract Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the naïve MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.

scholarly journals The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C)-priming through promoting the expression of indoleamine 2,3-dioxygenase.

2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  
Keyword(s):  
Weight Loss ◽  
Disease Activity ◽  
Stromal Cells ◽  
Therapeutic Efficacy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Poly I:C ◽  
Colon Tissue ◽  
Ifn Γ

Abstract Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.

scholarly journals Poly(I:c)-priming Improved the Therapeutic Efficacy of Mesenchymal Stromal Cells on Experimental Colitis by Promoting the Expression of Indoleamine 2,3-dioxygenase

2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  
Keyword(s):  
Weight Loss ◽  
Disease Activity ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Efficacy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Poly I:C ◽  
Colon Tissue

Abstract Background:Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods:To compare the therapeutic effects between the naïve MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfatein drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were significantly improved after injection of the primed MSCs. Results:Mice receiving the poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.

scholarly journals Ixeris dentataNAKAI Reduces Clinical Score and HIF-1 Expression in Experimental Colitis in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Dae-Seung Kim ◽  
Jang-Ho Ko ◽  
Yong-Deok Jeon ◽  
Yo-Han Han ◽  
Hyun-Ju Kim ◽  
...  
Keyword(s):  
Weight Loss ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Clinical Signs ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Inflammatory Cells ◽  
Clinical Score ◽  
Colon Tissue

Ixeris dentata(ID) is an herbal medicine used in Asian countries to treat indigestion, pneumonia, hepatitis, contusions, and tumors; however, its effect on intestinal inflammation is unknown. Thus, we investigated the effect of ID in the dextran sulfate sodium (DSS) model of colitis in female BALB/c mice; animals were evaluated after seven days of DSS treatment. DSS-treated mice showed considerable clinical signs, including weight loss, reduced colon length, colonic epithelial injury, infiltration of inflammatory cells in the colon tissue, and upregulation of inflammatory mediators. However, administration of ID attenuated body weight loss, colon shortening, and the increase in disease activity index score. ID also significantly decreased the colonic mucosal injury and the number of infiltrating mast cells. Moreover, ID inhibited the expressions of cyclooxygenase-2 and hypoxia-inducible factor-1αin colon tissue. Taken together, the results provide experimental evidence that ID might be a useful therapy for patients with ulcerative colitis.

scholarly journals Beneficial Effect of Shikonin on Experimental Colitis Induced by Dextran Sulfate Sodium in Balb/C Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Isabel Andújar ◽  
José Luis Ríos ◽  
Rosa María Giner ◽  
José Miguel Cerdá ◽  
María del Carmen Recio
Keyword(s):  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Myeloperoxidase Activity ◽  
Dependent Manner ◽  
Inflammatory Bowel ◽  
Activity Index Score ◽  
Bloody Stools ◽  
Dose Dependent

The naphthoquinone shikonin, a major component of the root ofLithospermum erythrorhizon, now is studied as an anti-inflammatory agent in the treatment of ulcerative colitis (UC). Acute UC was induced in Balb/C mice by oral administration of 5% dextran sodium sulfate (DSS). The disease activity index was evaluated, and a histologic study was carried out. Orally administered shikonin reduces induced UC in a dose-dependent manner, preventing the shortening of the colorectum and decreasing weight loss by 5% while improving the appearance of feces and preventing bloody stools. The disease activity index score was much lower in shikonin-treated mice than in the colitic group, as well as the myeloperoxidase activity. The expression of cyclooxygenase-2 was reduced by 75%, activation of NF-κB was reduced by 44%, and that of pSTAT-3 by 47%, as well as TNF-α, IL-1β, and IL-6 production. Similar results were obtained in primary macrophages culture. This is the first report of shikonin’s ability to attenuate acute UC induced by DSS. Shikonin acts by blocking the activation of two major targets: NF-κB and STAT-3, and thus constitutes a promising potential therapeutic agent for the management of the inflammatory bowel disease.

scholarly journals P015 Tricellulin overexpression protects against elevated macromolecule uptake in DSS colitis mice

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
F WEIß ◽  
I F M Lee ◽  
A Fromm ◽  
J C E Hu ◽  
T Breiderhoff ◽  
...  
Keyword(s):  
Weight Loss ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Sodium Sulphate ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Central Tube ◽  
Dss Colitis ◽  
Inflammatory Processes

Abstract Background In Inflammatory bowel disease, intestinal homeostasis cannot be sustained due to an overreaction of the immune system and a disturbed epithelial barrier due to an impaired tight junction (TJ). At tricellular TJs (tTJs), which are formed where three cells meet, the TJ network is basolaterally expanded and forms a central tube which would be potentially large enough to allow for a paracellular passage of macromolecules. Under normal conditions, the tTJ protein tricellulin (Tric) seals the central tube against luminal uptake. However, in ulcerative colitis (UC), Tric is downregulated, resulting in increased uptake of macromolecules including antigens which may further support the inflammatory processes. Thus, we aimed to identify whether or not overexpression of Tric has a protective effect against inflammation. Methods We generated intestinal epithelial cell-specific overexpression of Tric in mice (B6.C-Tg(Vil-cre) Rosa26tgGFP-Tric). In Tric-overexpressing (Tric-OE) and in wild-type (wt) mice experimental colitis was induced by 3% dextran sodium sulphate (DSS) for 6 days. The effect was assessed by determining the disease activity index (DAI: weight loss, stool consistency, and stool bleeding) and the colon dimensions. Using chamber experiments were performed to determine permeabilities for ions and macromolecules of different sizes (4 and 10 kDa). Results No difference in weight loss was observed between wt and Tric-OE mice upon DSS treatment. However, Tric-OE mice suffered less from diarrhoea and had less bloody stools compared with wt mice resulting in a lower DAI. In addition, DSS caused a reduced colon length which was less prominent in Tric-OE mice than in wt mice. Functional analysis revealed higher permeabilities for Na+ and Cl− after DSS treatment with no significant differences between Tric-OE and wt mice. In contrast, permeabilities for macromolecules of both sizes were unchanged after DSS treatment in Tric-OE mice but elevated in wt-mice. Conclusion Tric-overexpression prevents the epithelial barrier from elevated paracellular uptake of macromolecules during DSS colitis without affecting ion permeability. This protects against DSS colitis as indicated by less affected clinical and structural outcome parameters, most likely via a reduction in a load of immunologically active macromolecules in the subepithelium.

scholarly journals Preventive Effect of Cardiotrophin-1 Administration before DSS-Induced Ulcerative Colitis in Mice

2019 ◽  
Vol 8 (12) ◽  
pp. 2086 ◽  
Author(s):  
Ana I. Sánchez-Garrido ◽  
Vanessa Prieto-Vicente ◽  
Víctor Blanco-Gozalo ◽  
Miguel Arévalo ◽  
Yaremi Quiros ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Course ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Tnf Α ◽  
Current Therapies ◽  
Ifn Γ ◽  
Histology And Immunohistochemistry

Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.

scholarly journals Traditional Chinese Medicine QPYF as Preventive Treatment forClostridium difficileAssociated Diarrhea in a Mouse Model

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Guo Ya-Nan ◽  
Wang Jun ◽  
Zhang Hao-Jun ◽  
Jia Hong-Bing ◽  
Li Ping ◽  
...  
Keyword(s):  
Weight Loss ◽  
Chinese Medicine ◽  
Clostridium Difficile ◽  
Traditional Chinese Medicine ◽  
Mouse Model ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Good Effect ◽  
Model Control

Traditional Chinese medicine QPYF has a good effect for treating antibiotic-associated diarrhea in clinical practice. The aim of this study is to test its efficacy to preventClostridium difficileassociated diarrhea (CDAD) in a mouse model. C57BL/6 mice were infected withClostridium difficileVPI 10463 after exposure to antimicrobial mixture. QPYF was administered from 7 days prior toClostridium difficileinfection to 20 days after infection, and its effect was compared with no treatment and receiving placebo. The mice were monitored for 20 days and the percent survival, disease activity index, weight loss, colon histopathology, and the levels of toxins in the feces were measured. The expressions of TNFα, MCP-1, NF-κB p65, and phospho-NF-κB p65 in the colon were presented by immunohistochemistry. The survival rate of QPYF group (93.75%) was higher than that of model control group (65%). The mice treated with QPYF had a lower weight loss and disease activity index, compared to the mice with placebo. A significantly lower level of histopathology scores, toxins in the feces, and TNFα, MCP-1, NF-κB p65, and phospho-NF-κB p65 were detected for QPYF-treated mice. Traditional Chinese medicine QPYF showed a good preventive effect for CDAD in a mouse model.

scholarly journals Boehmeria niveaAttenuates the Development of Dextran Sulfate Sodium-Induced Experimental Colitis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Eun Ju Shin ◽  
Mi Jeong Sung ◽  
Hye Jeong Yang ◽  
Myung Sunny Kim ◽  
Jin-Taek Hwang
Keyword(s):  
Activity Index ◽  
Disease Activity Index ◽  
Ethanol Extract ◽  
Experimental Colitis ◽  
Control Group ◽  
Untreated Control Group ◽  
Colon Tissue ◽  
Chemotactic Protein ◽  
Cox 2 ◽  
Histopathological Score

We examined the therapeutic effect of an ethanol extract derived fromBoehmeria nivea(Linn.) Gaudich in a mouse model of experimental colitis. Treatment with 70% ethanol extract derived fromB. nivea(EBN) at a dose of 100, 200, or 500 mg/(kg·d) improved colon shortening, body weight, the disease activity index (DAI), and histopathological score of DSS-induced colitis mice. DSS significantly increased the levels of cyclooxygenase-(COX-) 2 in colon tissue relative to that of the untreated control group. EBN administered at 100, 200, or 500 mg/(kg·d) reduced COX-2 levels in the DSS-treated mice. In addition, EBN decreased the DSS-induced secretion of the inflammatory cytokine interleukin-6 (IL-6) and chemokine monocyte chemotactic protein-1 (MCP-1). Taken together, these data suggest thatB. niveaextract is effective in preventing colitis.

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