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Ulcerative colitis (UC) is a persistent inflammatory intestinal disease that consistently affects the colon and rectum. Its exact cause remains unknown. UC causes a considerable challenge in healthcare, prompting research for novel therapeutic strategies. Although probiotics have gained popularity as possible candidates for managing UC, studies are still ongoing to identify the best probiotics or probiotic mixtures for clinical applications. This study aimed to determine the efficacy of a multi-strain probiotic mixture in mitigating intestinal inflammation in a colitis mouse model induced by dextran sulfate sodium. Specifically, a multi-strain probiotic mixture consisting of Tetragenococcus halophilus and Eubacterium rectale was used to study its impact on colitis symptoms. Anti-inflammatory effects were evaluated using ELISA and flow cytometry. The configuration of gut microbial communities was determined using 16S rRNA metagenomic analysis. According to this study, colitis mice treated with the probiotic mixture experienced reduced weight loss and significantly less colonic shortening compared to untreated mice. Additionally, the treated mice exhibited increased levels of forkhead box P3 (Foxp3) and interleukin 10, along with decreased expression of dendritic cell activation markers, such as CD40+, CD80+, and CD83+, in peripheral blood leukocytes and intraepithelial lymphocytes. Furthermore, there was a significant decrease in the frequencies of CD8+N.K1.1+ cells and CD11b+Ly6G+ cells. In terms of the gut microbiota, probiotic-mixture treatment of colitis mice significantly increased the abundance of the phyla Actinobacteria and Verrucomicrobia (p < 0.05). These results provide valuable insights into the therapeutic promise of multi-strain probiotics, shedding light on their potential to alleviate colitis symptoms. This research contributes to the ongoing exploration of effective probiotic interventions for managing inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Abstract Background It has been suggested that the HLA-G molecule is a genetic risk factor for Behcet's disease (BD). In this study, we evaluated the level of Qa-2, a murine nonclassical class I MHC molecule and possible functional homolog of HLA-G, to determine if it was associated with various symptoms of BD-like mice. In addition, we investigated siRNA (small interfering RNA) treatment to determine if it inhibited Qa-2 expression, thereby changing the symptoms of mice. Methods RNA interference (RNAi) and vector transfection were employed to manipulate gene expression in vivo in mice. siRNA (small interfering RNA) or Qa-2 expression vector was applied to inhibit or up-regulate Qa-2 expression, respectively. Results The Qa-2 levels in granulocytes were lower in BD-like mice than in normal controls. The silencing of Qa-2 by intravenous injection of siRNA (500 nmol/mouse, 4 times at 3-day intervals) specifically reduced the Qa-2 levels and worsened the BD-like symptoms. Conclusions Silencing Qa-2 by injecting siRNA into mice resulted in deterioration of symptoms in BD-like mice.

Summary: Background: Anti-TNFα antibodies have been used for treating inflammation in patients. But, more effective and safer drugs need to be developed for improved future therapeutic use. Objectives: To inhibit the expression of TNFα, we used small interfering RNAs (siRNAs) to reduce over expression of TNFαin vitro in cell cultures and in an in vivo Behcet''s disease-like (BD) mouse model for amelioration of chronic inflammation. Methods: TNFα siRNA was injected intraperitoneally twice with a 1-week interval. To compare the efficacy of TNFα siRNA versus an anti-TNFα antibody, Infliximab and Etanercept were administered to symptomatic mice with inflamed tissue. Results: Intraperitoneal delivery of TNFα siRNA effectively decreased BD symptoms in 18 of 32 cases (56.3%). Scrambled siRNA treatment decreased BD symptoms in 2 of 19 cases (10.5%). Infliximab was effective in 11 of 27 cases (40.7%) and Etanercept was also effective in 9 of 25 cases (36.0%) at the end of the second week after treatment. TNFα siRNA reduced serum levels of TNFα (1.57±0.43pg/ml), compared to levels in mice not injected (84.02±24.59pg/ml) (p <0.01) or scramble injected (118.89±20.08pg/ml) (p <0.01). After single injection of TNFα siRNA, improvement of BD symptoms showed at 9±7th day on an average, contrary, in Infliximab injected group, improvement was apparent at 15±4th day after injection (p <0.05). Conclusion: We show that siRNAs can be employed to inhibit cytokine gene expression in an in vivo disease mouse model. This inhibition may, therefore, be attributed to the improvement of inflammatory symptoms. [Copyright &y& Elsevier]

CD206 is a macrophage mannose receptor involved in variety of autoimmune and inflammatory diseases. This study aimed to identify the pathogenic role of CD206 in a herpes simplex virus (HSV) induced Behçet's disease (BD) mouse model. CD206 positive cells were detected in peripheral blood mononuclear cells and quantified by flow cytometry. Levels of cytokines were measured by ELISA. CD206 was found to be down-regulated both in vitro (10 -6 M) and in vivo (200μg/mouse) after treatment with N-acetylgalactosamine (GalNAc), a ligand for CD206. The down-regulation of CD206 was correlated with improvement in BD symptoms. Colchicine (2μg/mouse) or pentoxifylline (400μg/mouse) treated mice displayed improvement in BD symptoms with fewer CD206 positive cells. The prevalence of CD206-positive cells differed between ligand-responsive and non-responsive BD mice. Inhibition of CD206 was associated with down-regulated serum level of interleukin-17 in GalNAc-treated BD mice. These results suggest that the expression of CD206 is correlated with HSV-induced BD symptoms in mice, implicating that CD206 might have a pathogenic role in BD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: This study was conducted to understand the role of vitamin D3 through the regulation of Toll like receptors (TLRs) and cytokines in herpes simplex virus-induced Behçet's disease (BD)-like mice., Methods: Serum 25-hydroxyvitamin D (1,25(OH)2D3) levels were measured in BD-like mice, as well as virus injected and asymptomatic appearance BD normal mice (BDN). The frequencies of TLRs of peritoneal macrophages were compared by FACS. To determine the effect of vitamin D3 in vitro, peritoneal macrophages were isolated and then incubated with 1,25(OH)2D3. To identify the mechanism of improvement of BD-like symptoms induced by 1,25(OH)2D3, mice were orally administered 1,25(OH)2D3., Results: The serum 25-hydroxyvitamin D levels in BD-like mice were 12.4 ± 5.4ng/ml, while they were 17.5 ± 7.2ng/ml in BDN mice. The frequency of TLR2 in BD-like mice was 32.91 ± 20.88%, while it was 12.73 ± 7.67% in BDN. The frequency of TLR4 was 26.09 ± 10.20% in BD-like mice and 9.72 ± 5.30% in BDN. In a 72 h culture of peritoneal macrophages in 10-8 M 1,25(OH)2D3, the frequency of TLR2 was 25.0 ± 2.7%, while it was 37.3 ± 5.8% in the control group. The frequency of TLR4 was 18.9 ± 5.3% with 1,25(OH)2D3, while it was 30.3 ± 0.1% in the control group. Treatment with 1,25(OH)2D3 improved the symptoms in six out of 11 BD-like mice and downregulated the frequency of TLR2 and TLR4. Moreover, 1,25(OH)2D3 influenced Interleukin-6 and TNF-alpha expression in the sera of BD-like mice., Conclusions: Vitamin D improved BD-like symptoms by down-regulating the expression of TLRs and pro-inflammatory cytokines in in vivo mouse models.