scholarly journals Recombinant Human Soluble Thrombomodulin Suppresses Arteritis in a Mouse Model of Kawasaki Disease

2021 ◽  
Author(s):  
Hironobu Nakayama ◽  
Hiroyasu Inada ◽  
Tatsuya Inukai ◽  
Kenta Kondo ◽  
Kazuyuki Hirai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kawasaki Disease ◽  
Mouse Model ◽  
Inflammatory Cytokine ◽  
Water Soluble ◽  
Ivig Treatment ◽  
Soluble Thrombomodulin ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Recombinant Human Soluble Thrombomodulin

Abstract Background: Kawasaki Disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and mainly affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, and they are at an increased risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulation, anti-inflammatory and cytoprotective properties, on the development of coronary arteritis in a mouse model of vasculitis. Methods: To prepare an animal model of KD-like vasculitis, Candida albicans water-soluble fraction (CAWS) was intraperitoneally injected into DBA/2 mice for 5 consecutive days, and then rTM (0, 0.2, 1, and 4 mg/kg body weight) was injected. rTM administration was performed at two intervals: one is for 10 consecutive days from the first day and the other is for 5 consecutive days from the 1st to 15th days. Histopathological analysis of the heart was performed 20, 27, 34, and 48 days after CAWS treatment, and the gene expression of anti-inflammatory cytokine interleukin-10 (IL-10), pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), and tissue factor (TF) in the heart and spleen was investigated.Results: Five consecutive doses of rTM (4 mg/kg) from 1 to 14 days after CAWS treatment significantly suppressed cardiac hypertrophy and arteritis by 34 days after CAWS treatment. The gene expression analysis of samples prepared from the heart and spleen of mice treated with CAWS and/or rTM showed that rTM administration increased the level of IL-10 in the heart. This increase was observed until day 27 and was not observed thereafter. The expression of TNF-α was observed in the heart of mice treated with CAWS and was not altered by rTM treatment. However, in the spleen, CAWS treatment reduced the IL-10 level and increased the TF level, whereas rTM treatment restored normal levels of both factors.Conclusions: These findings suggest that rTM specifically increases IL-10, decreases TF, and suppresses CAWS-induced vasculitis without affecting TNF-α production. Therefore, rTM can be used as a treatment for KD.

Recombinant Human Soluble Thrombomodulin Suppresses Arteritis in a Mouse Model of Kawasaki Disease

2021 ◽  
pp. 1-13
Author(s):  
Hironobu Nakayama ◽  
Hiroyasu Inada ◽  
Tatsuya Inukai ◽  
Kenta Kondo ◽  
Kazuyuki Hirai ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Mouse Model ◽  
Mrna Expression ◽  
Systemic Vasculitis ◽  
Water Soluble ◽  
Ivig Treatment ◽  
Soluble Thrombomodulin ◽  
Coronary Aneurysms ◽  
Tnf Α ◽  
Recombinant Human Soluble Thrombomodulin

<b><i>Introduction and Objective:</i></b> Kawasaki disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and primarily affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, which increases their risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulant, anti-inflammatory, and cytoprotective properties on the development of coronary arteritis in a mouse model of vasculitis. <b><i>Methods:</i></b> An animal model of KD-like vasculitis was created by injecting mice with <i>Candida albicans</i> water-soluble fraction (CAWS). This model was used to investigate the mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-α), and tissue factor (TF), in addition to histopathology of heart tissues. <b><i>Results:</i></b> rTM treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 days after CAWS treatment. In addition, mRNA expression analysis revealed that rTM administration increased cardiac IL-10 expression until day 27, whereas expression of TNF-α was unaffected. Moreover, in the spleen, rTM treatment restores IL-10 and TF expression to normal levels. <b><i>Conclusion:</i></b> These findings suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. Therefore, rTM may be an effective treatment for KD.

scholarly journals Camel milk Whey Inhibits Inflammatory Colorectal Cancer Development Via Down regulation of Pro-inflammatory Cytokines in Induced AOM/DSS Mouse Model

2019 ◽  
pp. 256 ◽  
Author(s):  
Mariam M. Al-Omari ◽  
Razan B. Al-Ghariebeh, Abed Alkarem Abu Alhaija ◽  
Heba Al- Zoubi ◽  
Khaled M. Al-Qaoud
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Camel Milk ◽  
Cytokine Gene Expression ◽  
Milk Whey ◽  
Potential Activity ◽  
Ifn Γ ◽  
Anti Inflammatory

Camel milk (CM) has got an increasing interest by traditional healers and medical practitioners in areas where camels are raised for their therapeutic potential. To investigate the potential activity of CM against cancer on scientific bases, azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) colitis Balb/c mouse model of CRC was used and CM whey was given orally during disease development. Colitis associated symptoms and tumor development were followed during the experiment and at the day of termination. Pro-inflammatory and anti-inflammatory cytokine gene expression were quantified using qPCR. The results showed a significant effect for CM whey on the reduction of early stage development of CRC and colon inflammation symptoms, as revealed by enhanced weight gain, reduced bloody stool and diarrhea. A concurrent reduction in gene expression of the inflammatory cytokine IL-6 was evident in colon tissue of CM whey treated mice. Moreover, both IFN-γ and IL-8 gene expression was also significantly reduced in treated mice. On the contrary, the expression of anti-inflammatory cytokines IL-10 was elevated in colon tissues of CM treated mice. In addition, iNOS, a marker for inflamed mucosa was down-regulated in treated mice. A control bovine milk whey treated group showed similar effect on IL-8, IL-6 and iNOS gene expression, whereas an elevation in IFN-γ was noticed in this group. Our results indicate the potential activity of CM whey in reducing the development of CRC in mice mainly by reducing colitis induction by chemical stimuli. Whether the active substance responsible for this activity is single or combined deserves further investigation.

scholarly journals Inflammation modulates regeneration in the acute or chronically damaged zebrafish retina

2021 ◽  
Author(s):  
Maria Iribarne ◽  
David Hyde
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokine ◽  
Gold Rush ◽  
Cytokine Gene Expression ◽  
Retinal Damage ◽  
Cytokine Gene ◽  
Reactive Microglia ◽  
Cytokine Genes ◽  
Tnf Α ◽  
Anti Inflammatory

Unlike mammals, zebrafish regenerate in response to retinal damage. Because microglia are activated by retinal damage, we investigated their role during regeneration following acute or chronic damage. At three weeks-post-fertilization (wpf), fish exhibiting NMDA-induced acute damage or cone photoreceptor-specific chronic degeneration, the gold rush (gosh) mutant, displayed reactive microglia and Müller glia proliferation. Retinas treated to inhibit the immune response lacked reactive microglia and possessed fewer PCNA-positive cells, while LPS treatment increased microglia and PCNA-labeled cells. NMDA-injured retinas upregulated the expression of il-1β and tnf-α pro-inflammatory cytokine genes, followed by increased expression of il-10 and arg1 anti-inflammatory/remodeling cytokine genes. An early and transiently TNF-α pro-inflammatory microglia population was identified in the NMDA-damaged retina. In contrast, gosh mutant retinas exhibited a mild increase of pro-inflammatory cytokine gene expression concurrently with a greater increased in anti-inflammatory/remodeling cytokine gene expression. Few TNF-α pro-inflammatory microglia were observed in the gosh retina. How inflammation regulates regeneration in zebrafish would provide important clues towards improving the therapeutic strategies for repairing injured mammalian tissues.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P&lt;0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Amino acid sequences characterization and anti-inflammatory potency evaluation of Portulaca oleracea L. oligopeptides in macrophages

RSC Advances ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 7321-7327
Author(s):  
Shihui Chang ◽  
Liping Wang ◽  
Ting Zhang ◽  
Yan Nie ◽  
Ruijie Liu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Cytokine Expression ◽  
Amino Acid Sequences ◽  
Portulaca Oleracea ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

POP-1 performed excellent anti-inflammatory potency by attenuating the pro-inflammatory cytokine expression (TNF-α, NO, IL-1β); inhibiting iNOS and COX-2 expressions and regulating the MAPK, PI3K/Akt and NF-κB signaling pathways.

scholarly journals Microarray Based Functional Analysis of Myricetin and Proteomic Study on Its Anti-Inflammatory Property

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Tao Li ◽  
Jihe Zhu ◽  
Fangming Deng ◽  
Weiguo Wu ◽  
Zhibing Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Disease ◽  
Microarray Data ◽  
Inflammatory Cytokine ◽  
Gene Expressions ◽  
Genome Wide ◽  
Proteomic Study ◽  
Anti Inflammatory ◽  
First Time

Myricetin has been reported as a promising chemopreventive compound with multiple biofunctions. To evaluate its influence on gene expressions in genome-wide set and further investigate its anti-inflammatory property, the present study performed Gene Ontology and Ingenuity Pathway Analysis (IPA) to describe the basic gene expression characteristics by myricetin treatment in HepG2 cells, confirmed its multi-biofunction by real-time fluorescent quantitative PCR (RT-qPCR), and further verified its anti-inflammatory property by Western blotting and bio-plex-based cytokines assay. The IPA data showed that 337 gene expressions (48% of the top molecules) are disturbed over 2-fold, and the most possible biofunctions of myricetin are the effect on “cardiovascular disease, metabolic disease, and lipid metabolism,” via regulation of 28 molecules with statistic score of 46. RT-qPCR data confirmed the accuracy of microarray data, and cytokines assay results indicated that 6 of the total 27 inflammatory cytokine secretions were significantly inhibited by myricetin pretreatment, including TNF-α, IFN-γ, IL-1α, IL-1β, IL-2, and IL-6. The present study is the first time to elucidate the multi-function of myricetin in genome-wide set by IPA analysis and verify its anti-inflammatory property by proteomics of cytokines assay. Therefore, these results enrich the comprehensive bioactivities of myricetin and reveal that myricetin has powerful anti-inflammatory property, which provides encouragement for in vivo studies to verify its possible health benefits.

scholarly journals GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease

2016 ◽  
Vol 213 (10) ◽  
pp. 1983-1998 ◽  
Author(s):  
Angus T. Stock ◽  
Jacinta A. Hansen ◽  
Matthew A. Sleeman ◽  
Brent S. McKenzie ◽  
Ian P. Wicks
Keyword(s):  
Kawasaki Disease ◽  
Mouse Model ◽  
Immune Cell ◽  
Cardiac Fibroblasts ◽  
Developed Countries ◽  
Water Soluble ◽  
Cardiac Inflammation ◽  
Gm Csf ◽  
Cytokines And Chemokines ◽  
Macrophage Colony

Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD.

Effects of HSP70.1/3 gene knockout on acute respiratory distress syndrome and the inflammatory response following sepsis

2006 ◽  
Vol 290 (5) ◽  
pp. L956-L961 ◽  
Author(s):  
Kristen D. Singleton ◽  
Paul E. Wischmeyer
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Lung Tissue ◽  
Inflammatory Cytokine ◽  
Gene Knockout ◽  
Cecal Ligation ◽  
Hsp70 Expression ◽  
Experimental Sepsis ◽  
Hsp70 Gene ◽  
Tnf Α

Heat shock response has been implicated in attenuating NF-κB activation and inflammation following sepsis. Studies utilizing sublethal heat stress or chemical enhancers to induce in vivo HSP70 expression have demonstrated survival benefit after experimental sepsis. However, it is likely these methods of manipulating HSP70 expression have effects on other stress proteins. The aim of this study was to evaluate the role of specific deletion of HSP70.1/3 gene expression on ARDS, NF-κB activation, inflammatory cytokine expression, and survival following sepsis. To address this question, we induced sepsis in HSP70.1/3 KO and HSP70.1/3 WT mice via cecal ligation and puncture (CLP). We evaluated lung tissue NF-κB activation and TNF-α protein expression at 1 and 2 h, IL-6 protein expression at 1, 2, and 6, and lung histopathology 24 h after sepsis initiation. Survival was assessed for 5 days post-CLP. NF-κB activation in lung tissue was increased in HSP70.1/3(−/−) mice at all time points after sepsis initiation. Deletion of HSP70.1/3 prolonged NF-κB binding/activation in lung tissue. Peak expression of lung TNF-α at 1 and 2 h was also significantly increased in HSP70.1/3(−/−) mice. Expression of IL-6 was significantly increased at 2 and 6 h, and histopathology revealed a significant increase in lung injury in HSP70.1/3(−/−) mice. Last, deletion of the HSP70 gene led to increased mortality 5 days after sepsis initiation. These data reveal that absence of HSP70 alone can significantly increase ARDS, activation of NF-κB, and inflammatory cytokine response. The specific absence of HSP70 gene expression also leads to increased mortality after septic insult.

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