scholarly journals The CD200 Regulates Inflammation in Mice Independently of TNF-α Production

2021 ◽  
Vol 22 (10) ◽  
pp. 5358
Author(s):  
Katarzyna Tonecka ◽  
Agata Braniewska ◽  
Zofia Pilch ◽  
Zuzanna Sas ◽  
Marcin Skorzynski ◽  
...  
Keyword(s):  
Immune Cells ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Histological Evaluation ◽  
Bodyweight Loss ◽  
Colon Tissue ◽  
Tnf Α

Inflammatory bowel disease is characterized by the infiltration of immune cells and chronic inflammation. The immune inhibitory receptor, CD200R, is involved in the downregulation of the activation of immune cells to prevent excessive inflammation. We aimed to define the role of CD200R ligand-CD200 in the experimental model of intestinal inflammation in conventionally-reared mice. Mice were given a dextran sodium sulfate solution in drinking water. Bodyweight loss was monitored daily and the disease activity index was calculated, and a histological evaluation of the colon was performed. TNF-α production was measured in the culture of small fragments of the distal colon or bone marrow-derived macrophages (BMDMs) cocultured with CD200+ cells. We found that Cd200−/− mice displayed diminished severity of colitis when compared to WT mice. Inflammation significantly diminished CD200 expression in WT mice, particularly on vascular endothelial cells and immune cells. The co-culture of BMDMs with CD200+ cells inhibited TNF-α secretion. In vivo, acute colitis induced by DSS significantly increased TNF-α secretion in colon tissue in comparison to untreated controls. However, Cd200−/− mice secreted a similar level of TNF-α to WT mice in vivo. CD200 regulates the severity of DSS-induced colitis in conventionally-reared mice. The presence of CD200+ cells decreases TNF-α production by macrophages in vitro. However, during DDS-induced intestinal inflammation secretion of TNF-α is independent of CD200 expression.

scholarly journals Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zengjie Zheng ◽  
Hailong Jiang ◽  
Yan Huang ◽  
Jie Wang ◽  
Lei Qiu ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Activity Index ◽  
Tumor Necrosis Factor Receptor ◽  
Disease Activity Index ◽  
Acute Colitis ◽  
Surface Plasmon Resonance Analysis ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases.

scholarly journals The Bisindole Alkaloid Caulerpin, from Seaweeds of the Genus Caulerpa, Attenuated Colon Damage in Murine Colitis Model

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 318 ◽  
Author(s):  
Alessandra Lucena ◽  
Cássio Souza ◽  
Jéssica Jales ◽  
Paulo Guedes ◽  
George de Miranda ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Activity Index ◽  
Disease Activity Index ◽  
Colon Tissue ◽  
Inflammatory Infiltration ◽  
Tissue Samples ◽  
Murine Colitis ◽  
Tnf Α ◽  
Effective Doses

Caulerpin (CLP), an alkaloid from algae of the genus Caulerpa, has shown anti-inflammatory activity. Therefore, this study aimed to analyze the effect of CLP in the murine model of peritonitis and ulcerative colitis. Firstly, the mice were submitted to peritonitis to evaluate which dose of CLP (40, 4, or 0.4 mg/kg) could decrease the inflammatory infiltration in the peritoneum. The most effective doses were 40 and 4 mg/kg. Then, C57BL/6 mice were submitted to colitis development with 3% dextran sulfate sodium (DSS) and treated with CLP at doses of 40 and 4 mg/kg. The disease development was analyzed through the disease activity index (DAI); furthermore, colonic tissue samples were submitted to histological analysis, NFκB determination, and in vitro culture for cytokines assay. Therefore, CLP at 4 mg/kg presented the best results, triggering improvement of DAI and attenuating the colon shortening and damage. This dose was able to reduce the TNF-α, IFN-γ, IL-6, IL-17, and NFκB p65 levels, and increased the levels of IL-10 in the colon tissue. Thus, CLP mice treatment at a dose of 4 mg/kg showed promising results in ameliorating the damage observed in the ulcerative colitis.

scholarly journals Direct signaling of TL1A-DR3 on fibroblasts induces intestinal fibrosis in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Noam Jacob ◽  
Kotaro Kumagai ◽  
Jay P. Abraham ◽  
Yosuke Shimodaira ◽  
Yuefang Ye ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Activity Index ◽  
Death Receptor ◽  
Disease Activity Index ◽  
Cell Types ◽  
Clinical Disease ◽  
Major Pathway ◽  
Intestinal Fibrosis

Abstract Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease, modulating the location and severity of inflammation and fibrosis. TL1A expression is increased in inflamed mucosa and associated with fibrostenosing Crohn’s disease. Tl1a-overexpression in mice causes spontaneous ileitis, and exacerbates induced proximal colitis and fibrosis. Intestinal fibroblasts express Death-receptor 3 (DR3; the only know receptor for TL1A) and stimulation with TL1A induces activation in vitro. However, the contribution of direct TL1A-DR3 activation on fibroblasts to fibrosis in vivo remains unknown. TL1A overexpressing naïve T cells were transferred into Rag−/− , Rag−/− mice lacking DR3 in all cell types (Rag−/−Dr3−/−), or Rag−/− mice lacking DR3 only on fibroblasts (Rag−/−Dr3∆Col1a2) to induce colitis and fibrosis, assessed by clinical disease activity index, intestinal inflammation, and collagen deposition. Rag−/− mice developed overt colitis with intestinal fibrostenosis. In contrast, Rag−/−Dr3−/− demonstrated decreased inflammation and fibrosis. Despite similar clinical disease and inflammation as Rag−/−, Rag−/−Dr3∆Col1a2 exhibited reduced intestinal fibrosis and attenuated fibroblast activation and migration. RNA-Sequencing of TL1A-stimulated fibroblasts identified Rho signal transduction as a major pathway activated by TL1A and inhibition of this pathway modulated TL1A-mediated fibroblast functions. Thus, direct TL1A signaling on fibroblasts promotes intestinal fibrosis in vivo. These results provide novel insight into profibrotic pathways mediated by TL1A paralleling its pro-inflammatory effects.

scholarly journals Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xinghan Zheng ◽  
Liting Mai ◽  
Tongtong Wang ◽  
Ying Xu ◽  
Zireng Su ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Activity Index ◽  
Disease Activity Index ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Colon Tissue ◽  
Epithelial Barrier Function ◽  
Brucea Javanica ◽  
Tnf Α ◽  
Brucea Javanica Oil

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.

scholarly journals l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiangbing Mao ◽  
Rui Sun ◽  
Qingxiang Wang ◽  
Daiwen Chen ◽  
Bing Yu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Activity Index ◽  
Control Diet ◽  
Average Daily Gain ◽  
Disease Activity Index ◽  
Inflammatory Cells ◽  
Feed Conversion ◽  
Enterocyte Apoptosis

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

scholarly journals Study on the mechanism of Indigo naturalis and its two main compounds (indigo and indirubin) in the treatment of ulcerative colitis based on TLR4/MyD88/NF-κB pathway and intestinal microorganisms

2020 ◽  
Author(s):  
Qi-yue Yang ◽  
Ya-nan He ◽  
Le-le Ma ◽  
Run-chun Xu ◽  
Nan Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Pathological Section ◽  
Inflammatory Cytokine Production ◽  
Tnf Α ◽  
Indigo Naturalis ◽  
Inflammation Cytokines

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB，TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.

scholarly journals Sustained suppression of IL-18 by employing a vaccine ameliorates intestinal inflammation in TNBS-induced murine colitis

2019 ◽  
Vol 5 (7) ◽  
pp. FSO405 ◽  
Author(s):  
Qingdong Guan ◽  
Richard Warrington ◽  
Sem Moreno ◽  
Gefei Qing ◽  
Carolyn Weiss ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Trinitrobenzene Sulfonic Acid ◽  
Colon Tissue ◽  
Murine Colitis ◽  
Virus Like Particle ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
In Vivo Effects

Aim: To develop IL-18 peptide-based virus-like particle vaccines that elicit autoantibodies against IL-18 and to evaluate the in vivo effects of the vaccines in murine colitis. Methods: Recombinant IL-18 vaccines were constructed, and the effects of the vaccines were evaluated in trinitrobenzene sulfonic acid-induced acute and chronic colitis in mice. Results: Two murine IL-18 peptide-based vaccines (A and D) were developed, which induced relative long-lasting specific antibodies against IL-18. Vaccine-immunized mouse antisera could partially block IL-18-induced IFN-γ production in vitro. Mice receiving vaccine D, not vaccine A, had a significant decrease in intestinal inflammation, collagen deposition and pro-inflammatory cytokine levels in colon tissue. Conclusion: IL-18 vaccine may provide a potential therapeutic approach in the treatment of Crohn’s disease.

Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation

2005 ◽  
Vol 288 (2) ◽  
pp. L317-L325 ◽  
Author(s):  
Branislava Janic ◽  
Todd M. Umstead ◽  
David S. Phelps ◽  
Joanna Floros
Keyword(s):  
Immune Cells ◽  
Cytokine Production ◽  
Cell Damage ◽  
Surfactant Protein ◽  
Proinflammatory Cytokine Production ◽  
Tnf Α ◽  
In Vitro Systems ◽  
Alveolar Proteinosis

Ozone (O3), a major component of air pollution and a strong oxidizing agent, can lead to lung injury associated with edema, inflammation, and epithelial cell damage. The effects of O3on pulmonary immune cells have been studied in various in vivo and in vitro systems. We have shown previously that O3exposure of surfactant protein (SP)-A decreases its ability to modulate proinflammatory cytokine production by cells of monocyte/macrophage lineage (THP-1 cells). In this report, we exposed THP-1 cells and/or native SP-A obtained from bronchoalveolar lavage of patients with alveolar proteinosis to O3and studied cytokine production and NF-κB signaling. The results showed 1) exposure of THP-1 cells to O3significantly decreased their ability to express TNF-α in response to SP-A; TNF-α production, under these conditions, was still significantly higher than basal (unstimulated) levels in filtered air-exposed THP-1 cells; 2) exposure of both THP-1 cells and SP-A to O3did not result in any significant differences in TNF-α expression compared with basal levels; 3) O3exposure of SP-A resulted in a decreased ability of SP-A to activate the NF-κB pathway, as assessed by the lack of significant increase and decrease of the nuclear p65 subunit of NF-κB and cytoplasmic IκBα, respectively; and 4) O3exposure of THP-1 cells resulted in a decrease in SP-A-mediated THP-1 cell responsiveness, which did not seem to be mediated via the classic NF-κB pathway. These findings indicate that O3exposure may mediate its effect on macrophage function both directly and indirectly (via SP-A oxidation) and by involving different mechanisms.

Immunoblockade of PSGL-1 attenuates established experimental murine colitis by reduction of leukocyte rolling

2004 ◽  
Vol 287 (1) ◽  
pp. G115-G124 ◽  
Author(s):  
Emile M. Rijcken ◽  
Mike G. Laukoetter ◽  
Christoph Anthoni ◽  
Stephanie Meier ◽  
Rudolf Mennigen ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Activity Index ◽  
Leukocyte Adhesion ◽  
Combined Treatment ◽  
Disease Activity Index ◽  
Leukocyte Recruitment ◽  
Leukocyte Rolling ◽  
Chronic Colitis ◽  
Adhesive Interactions

Recruitment of circulating leukocytes into the colonic tissue is a key feature of intestinal inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) and very late antigen-4 (VLA-4) are expressed on leukocytes and play an important role in leukocyte-endothelial cell adhesive interactions. We examined the effects of immunoneutralization of PSGL-1 and VLA-4 on leukocyte recruitment in vivo in the development and treatment of experimental colitis. Chronic colitis was induced in balb/c mice by oral administration of dextran sodium sulfate (DSS). Monoclonal antibodies 2PH1 (anti-PSGL-1) and PS/2 (anti-VLA-4) or the combination of both were injected intravenously, and leukocyte adhesion was observed for 60 min in colonic submucosal venules by intravital microscopy (IVM) under isoflurane/N2O anesthesia. In addition, mice with established colitis were treated by daily intraperitoneal injections of 2PH1, PS/2, or the combination of both over 5 days. Disease activity index (DAI), histology, and myeloperoxidase (MPO) levels were compared with sham-treated DSS controls. We found that 2PH1 reduced the number of rolling leukocytes (148.7 ± 29.8 vs. 36.9 ± 8.7/0.01 mm2/30 s, P < 0.05), whereas leukocyte velocity was increased (24.0 ± 3.6 vs. 127.8 ± 11.7 μm/s, P < 0.05). PS/2 reduced leukocyte rolling to a lesser extent. Leukocyte firm adhesion was not influenced by 2PH1 but was strongly reduced by PS/2 (24.1 ± 2 vs. 4.4 ± 0.9/0.01 mm2/30 s, P < 0.05). Combined application did not cause additional effects on leukocyte adhesion. Treatment of chronic colitis with 2PH1 or PS/2 reduced DAI, mucosal injury, and MPO levels significantly. Combined treatment led to a significantly better reduction of DAI (0.4 ± 0.1 vs. 2.1 ± 0.2 points) and histology (9.7 ± 0.9 vs. 21.4 ± 4.6 points). In conclusion, PSGL-1 and VLA-4 play an important role for leukocyte recruitment during intestinal inflammation. Therapeutic strategies designed to disrupt interactions mediated by PSGL-1 and/or VLA-4 may prove beneficial in treatment of chronic colitis.

scholarly journals Development of Anti-inflammatory Probiotic Limosilactobacillus reuteri EFEL6901 as Kimchi Starter: in vitro and In vivo Evidence

2021 ◽  
Vol 12 ◽  
Author(s):  
Hee Seo ◽  
Hyunbin Seong ◽  
Ga Yun Kim ◽  
Yu Mi Jo ◽  
Seong Won Cheon ◽  
...  
Keyword(s):  
Activity Index ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Short Chain Fatty Acids ◽  
Fermented Foods ◽  
Gut Health ◽  
Gut Barrier Function ◽  
Anti Inflammatory

The use of probiotic starters can improve the sensory and health-promoting properties of fermented foods. In this study, we developed an anti-inflammatory probiotic starter, Limosilactobacillus reuteri EFEL6901, for use in kimchi fermentation. The EFEL6901 strain was safe for use in foods and was stable under human gastrointestinal conditions. In in vitro experiments, EFEL6901 cells adhered well to colonic epithelial cells and decreased nitric oxide production in lipopolysaccharide-induced macrophages. In in vivo experiments, oral administration of EFEL6901 to DSS-induced colitis mice models significantly alleviated the observed colitis symptoms, prevented body weight loss, lowered the disease activity index score, and prevented colon length shortening. Analysis of these results indicated that EFEL6901 played a probiotic role by preventing the overproduction of pro-inflammatory cytokines, improving gut barrier function, and up-regulating the concentrations of short-chain fatty acids. In addition, EFEL6901 made a fast growth in a simulated kimchi juice and it synthesized similar amounts of metabolites in nabak-kimchi comparable to a commercial kimchi. This study demonstrates that EFEL6901 can be used as a suitable kimchi starter to promote gut health and product quality.

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