Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis

There is growing evidence for an interplay between inflammatory and coagulation pathways in acute and chronic inflammatory diseases. However, it remains unclear whether components of the coagulation pathway, such as tissue factor (TF), contribute to intestinal inflammation, and whether targeting TF will blunt the inflammatory cell recruitment, tissue injury, and enhanced thrombus formation that occur in experimental colitis. Mice were fed 3% dextran sodium sulfate (DSS) to induce colonic inflammation, with some mice receiving a mouse TF-blocking antibody (muTF-Ab). The adhesion of leukocytes and platelets in colonic venules, light/dye-induced thrombus formation in cremaster muscle microvessels, as well as disease activity index, thrombin–antithrombin (TAT) complexes in plasma, and histopathologic changes in the colonic mucosa were monitored in untreated and muTF-Ab–treated colitic mice. In untreated mice, DSS elicited the recruitment of adherent leukocytes and platelets in colonic venules, caused gross and histologic injury, increased plasma TAT complexes, and enhanced thrombus formation in muscle arterioles. muTF-Ab prevented elevation in TAT complexes, reduced blood cell recruitment and tissue injury, and blunted thrombus formation in DSS colitic mice. These findings implicate TF in intestinal inflammation and support an interaction between inflammation and coagulation in experimental colitis.

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miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1

Cells ◽

10.3390/cells11010058 ◽

2021 ◽

Vol 11 (1) ◽

pp. 58

Author(s):

Shafaque Rahman ◽

Jolien Vandewalle ◽

Patricia H. P. van Hamersveld ◽

Caroline Verseijden ◽

Olaf Welting ◽

...

Keyword(s):

Immune Responses ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Experimental Colitis ◽

Microbial Responses ◽

Index Weight ◽

Lower Disease Activity ◽

Deficient Mice

Antimicrobial responses play an important role in maintaining intestinal heath. Recently we reported that miR-511 may regulate TLR4 responses leading to enhanced intestinal inflammation. However, the exact mechanism remained unclear. In this study we investigated the effect of miR-511 deficiency on anti-microbial responses and DSS-induced intestinal inflammation. miR-511-deficient mice were protected from DSS-induced colitis as shown by significantly lower disease activity index, weight loss and histology scores in the miR-511-deficient group. Furthermore, reduced inflammatory cytokine responses were observed in colons of miR-511 deficient mice. In vitro studies with bone marrow-derived M2 macrophages showed reduced TLR3 and TLR4 responses in miR-511-deficient macrophages compared to WT macrophages. Subsequent RNA sequencing revealed Wdfy1 as the potential miR-511 target. WDFY1 deficiency is related to impaired TLR3/TLR4 immune responses and the expression was downregulated in miR-511-deficient macrophages and colons. Together, this study shows that miR-511 is involved in the regulation of intestinal inflammation through downstream regulation of TLR3 and TLR4 responses via Wdfy1.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/671281 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 8

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.

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A salmon peptide diet alleviates experimental colitis as compared with fish oil

Journal of Nutritional Science ◽

10.1017/jns.2012.23 ◽

2013 ◽

Vol 2 ◽

Cited By ~ 8

Author(s):

Tore Grimstad ◽

Bodil Bjørndal ◽

Daniel Cacabelos ◽

Ole G. Aasprong ◽

Roald Omdal ◽

...

Keyword(s):

Fish Oil ◽

Dietary Intervention ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Experimental Colitis ◽

Mrna Levels ◽

Keratinocyte Chemoattractant ◽

Male Wistar Rats ◽

Inflammatory Bowel

AbstractFish oil (FO) has been shown to have anti-inflammatory properties in animal models of inflammatory bowel disease, but how fish peptides (FP) influence intestinal inflammation has been less studied. Male Wistar rats, divided into five groups, were included in a 4-week dietary intervention study. Of the groups, four were exposed in the fourth week to 5 % dextran sulfate sodium (DSS) to induce colitis, while one group was unexposed. The diets were: (1) control, (2) control + DSS, (3) FO (5 %) + DSS, (4) FP (3·5 %) + DSS, (5) FO + FP + DSS. Following DSS intake, weight and disease activity index (DAI) were assessed, and histological combined score (HCS), selected colonic PG, cytokines, oxidative damage markers and mRNA levels were measured. FP reduced HCS, tended to lower DAI (P = 0·07) and reduced keratinocyte chemoattractant/growth-regulated oncogene levels, as compared with the FO diet. FP also reduced mRNA levels of Il-6 and Cxcl1, although not significantly. FO intake increased the DAI as compared with DSS alone. PGE3 levels increased after the FO diet, and even more following FO + FP intake. The FP diet seems to have a protective effect in DSS-induced colitis as compared with FO. A number of beneficial, but non-significant, changes also occurred after FP v. DSS. A combined FO + FP diet may influence PG synthesis, as PGE3 levels were higher after the combined diet than after FO alone.

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Safety of P28GST, a Protein Derived from a Schistosome Helminth Parasite, in Patients with Crohn’s Disease: A Pilot Study (ACROHNEM)

Journal of Clinical Medicine ◽

10.3390/jcm9010041 ◽

2019 ◽

Vol 9 (1) ◽

pp. 41 ◽

Cited By ~ 5

Author(s):

Monique Capron ◽

Laurent Béghin ◽

Céline Leclercq ◽

Julien Labreuche ◽

Arnaud Dendooven ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Inflammation ◽

Activity Index ◽

Therapeutic Option ◽

Disease Activity Index ◽

Experimental Colitis ◽

Open Label ◽

Th17 Response ◽

Clinical Recurrence

Despite the development of novel therapies, inflammatory bowel diseases remain an innovative treatment challenge. Helminth therapy is a new promising approach, and a key issue is the identification of helminth-derived anti-inflammatory mediators. P28 glutathione-S-transferase (P28GST), a protein derived from schistosomes, a trematode parasitic helminth, was shown to reduce intestinal inflammation in experimental colitis by down-regulating the Th1/Th17 response. In this multicenter, open-label, pilot Phase 2a study, we evaluated the safety of P28GST administered to patients with mild Crohn’s disease (CD). We enrolled 10 patients with a baseline Crohn’s disease activity index (CDAI) value <220. Eight patients received two to three subcutaneous injections of recombinant P28GST with adjuvant. This three-month treatment was followed by a nine-month monitoring period. The primary endpoints were the monthly rate and seriousness of adverse events (AEs). Secondary endpoints were clinical recurrence, assessed with the CDAI as well as the levels of immunologic and inflammatory blood and tissue markers. The most common AEs were local or regional events at the injection site and gastrointestinal disorders. At three months after the first injection, CDAI scores and blood calprotectin levels decreased in parallel. These results indicate that P28GST showed promise as a safe and new therapeutic option for treating CD.

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Dynamics of inflammatory cell recruitment in a cigarette smoke induced COPD mouse model

Pneumologie ◽

10.1055/s-0031-1296117 ◽

2011 ◽

Vol 65 (12) ◽

Author(s):

K Kohse ◽

G John ◽

O Eickelberg ◽

AÖ Yildirim

Keyword(s):

Mouse Model ◽

Cigarette Smoke ◽

Inflammatory Cell ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment

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Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

PLoS ONE ◽

10.1371/journal.pone.0145147 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0145147 ◽

Cited By ~ 7

Author(s):

Silvia Affò ◽

Daniel Rodrigo-Torres ◽

Delia Blaya ◽

Oriol Morales-Ibanez ◽

Mar Coll ◽

...

Keyword(s):

Chemokine Receptor ◽

Inflammatory Cell ◽

Liver Inflammation ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment

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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

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02087-7 ◽

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.

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Isolation and Characterization of Potentially Probiotic Bacterial Strains from Mice: Proof of Concept for Personalized Probiotics

Nutrients ◽

10.3390/nu10111684 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1684 ◽

Cited By ~ 2

Author(s):

Larissa Celiberto ◽

Roseli Pinto ◽

Elizeu Rossi ◽

Bruce Vallance ◽

Daniela Cavallini

Keyword(s):

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Bacterial Strains ◽

Dss Colitis ◽

Isolation And Characterization ◽

Inflammatory Bowel ◽

Commercial Probiotics ◽

Lower Disease Activity

Modulation of the gut microbiota through the use of probiotics has been widely used to treat or prevent several intestinal diseases. However, inconsistent results have compromised the efficacy of this approach, especially in severe conditions such as inflammatory bowel disease (IBD). The purpose of our study was to develop a personalized probiotic strategy and assess its efficacy in a murine model of intestinal inflammation. Commensal bacterial strains were isolated from the feces of healthy mice and then administered back to the host as a personalized treatment in dextran sodium sulfate (DSS)-induced colitis. Colonic tissues were collected for histological analysis and to investigate inflammatory markers such as Il-1β, Il-6, TGF-β, and Il-10, and the enzyme myeloperoxidase as a neutrophil marker. The group that received the personalized probiotic showed reduced susceptibility to DSS-colitis as compared to a commercial probiotic. This protection was characterized by a lower disease activity index and reduced histopathological damage in the colon. Moreover, the personalized probiotic was more effective in modulating the host immune response, leading to decreased Il-1β and Il-6 and increased TGF-β and Il-10 expression. In conclusion, our study suggests that personalized probiotics may possess an advantage over commercial probiotics in treating dysbiotic-related conditions, possibly because they are derived directly from the host’s own microbiota.

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The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01098-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 6317-6327 ◽

Cited By ~ 21

Author(s):

Hussein Traboulsi ◽

Alexandre Cloutier ◽

Kumaraswamy Boyapelly ◽

Marc-André Bonin ◽

Éric Marsault ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Inflammatory Response ◽

Lung Inflammation ◽

Inflammatory Cell ◽

Influenza Virus Infection ◽

Cytokine Gene Expression ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment ◽

Anti Inflammatory

ABSTRACTThe host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.

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