scholarly journals Chitosan Oligosaccharides Suppress Nuclear Factor-Kappa B Activation and Ameliorate Experimental Autoimmune Uveoretinitis in Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 8326
Author(s):  
Sheng-Min Hsu ◽  
Chang-Hao Yang ◽  
Hsien-Yang Tsai ◽  
Chia-Jhen Lin ◽  
Yi-Hsuan Fang ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Therapeutic Potential ◽  
Posterior Uveitis ◽  
High Dose ◽  
Experimental Autoimmune Uveoretinitis ◽  
Chitosan Oligosaccharides ◽  
Interphotoreceptor Retinoid Binding Protein ◽  
Tnf Α ◽  
Phosphate Buffered Saline ◽  
Experimental Autoimmune

We investigated the therapeutic potential and mechanism of chitosan oligosaccharides (COS) for experimental autoimmune uveoretinitis (EAU) in mice. EAU was induced in C57/BL6 mice by injection of human interphotoreceptor retinoid-binding protein (IRBP) peptides. At the same time, a high or low dose (20 or 10 mg/kg) of COS or phosphate-buffered saline (PBS) was given to mice daily after EAU induction. We found that mouse EAU is ameliorated by the high-dose COS treatment when compared with PBS treatment. In the retinas of high-dose COS-treated mice, the nuclear translocation of NF-κB subunit (p65) was suppressed, and the expression of several key EAU inflammatory mediators, IFN-γ, TNF-α, IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17 and MCP-1 was lowered. These results suggest that COS may be a potential treatment for posterior uveitis.

scholarly journals Intravenous Liposomal Prednisolone Downregulates In Situ TNF-α Production by T-cells in Experimental Autoimmune Encephalomyelitis

2003 ◽  
Vol 51 (9) ◽  
pp. 1241-1244 ◽  
Author(s):  
Jens Schmidt ◽  
Josbert M. Metselaar ◽  
Ralf Gold
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
High Dose ◽  
Autoimmune Encephalomyelitis ◽  
Double Labeling ◽  
Formalin Fixed Paraffin ◽  
Tnf Α ◽  
Formalin Fixed Paraffin Embedded ◽  
Factor Α ◽  
Experimental Autoimmune

Multiple sclerosis (MS) relapses are treated with high-dose IV glucocorticosteroids. Here we investigated mechanisms of long-circulating polyethylene glycol-coated liposomes encapsulating prednisolone (PL) in adoptive transfer experimental autoimmune encephalomyelitis. Rats received IV 10 mg/kg PL 6, 18, or 42 hr before sacrifice at disease maximum. In formalin-fixed, paraffin-embedded spinal cord we employed a nonfluorescent immunohistochemical (IHC) double labeling. We stained for tumor necrosis factor-α (TNF-α) in combination with a T-cell antigen. Compared with PBS-containing liposomes, PL at 18 hr, and more at 42 hr, significantly reduced the rate of TNF-α double-labeled T-cells. This correlated with an ameliorated disease score at day 5 after PL 42 hr. Our results help to further understand mechanisms of action of drug targeting by liposomal steroids, with possible implications for treatment of autoimmune disorders such as MS.

scholarly journals Chitosan Oligosaccharides Attenuate Ocular Inflammation in Rats with Experimental Autoimmune Anterior Uveitis

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
I-Mo Fang ◽  
Chang-Hao Yang ◽  
Chung-May Yang
Keyword(s):  
Inflammatory Mediators ◽  
Anterior Uveitis ◽  
Culture Media ◽  
High Dose ◽  
Dependent Manner ◽  
Protective Effects ◽  
Chitosan Oligosaccharides ◽  
Clinical Scores ◽  
Experimental Autoimmune Anterior Uveitis ◽  
Experimental Autoimmune

We investigated the protective effects and mechanisms of chitosan oligosaccharides (COS) on experimental autoimmune anterior uveitis (EAAU) in rats. EAAU was induced in Lewis rats by footpad and intraperitoneal injections of melanin-associated antigen. The rats received intraperitoneal injections of low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS daily after the immunization. The effects of COS were evaluated by determining the clinical scores and the morphology of the iris/ciliary body (ICB). The expression of inflammatory mediators was evaluated using western blot, immunofluorescence, and ELISA. Treatment with COS significantly attenuated the clinical scores and the leukocyte infiltration in the ICB in a dose-dependent manner. COS effectively reduced the expression of inflammatory mediators (TNF-α, iNOS, MCP-1, RANTES, fractalkine, and ICAM-1). Moreover, COS decreased the IκB degradation and p65 presence in the ICB, which resulted in the inhibition of NF-κB/DNA binding activity. In an in vitro study, sensitized spleen-derived lymphocytes of the COS-treated group showed less chemotaxis toward their aqueous humor and decreased secretion of the above inflammatory mediators in the culture media. COS treated EAAU by inhibiting the activation of NF-κB and reducing the expression of inflammatory mediators. COS might be a potential treatment for acute anterior uveitis.

scholarly journals Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 198 ◽  
Author(s):  
Ba-Wool Lee ◽  
Ji-Hye Ha ◽  
Han-Gyo Shin ◽  
Seong-Hun Jeong ◽  
Da-Bin Jeon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Herbal Remedy ◽  
Related Factor ◽  
Nuclear Factor ◽  
Tnf Α

Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.

TNF-alpha protects from exacerbated autoinflammatory response in mouse model of experimental autoimmune myocarditis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Rolski ◽  
K Weglarczyk ◽  
P Pelczar ◽  
M Siedlar ◽  
B Ludewig ◽  
...  
Keyword(s):  
T Cells ◽  
High Dose ◽  
Wild Type ◽  
Autoimmune Myocarditis ◽  
Heart Failure Patients ◽  
Tnf Α ◽  
Intercellular Adhesion Molecules ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Abstract Background Myocarditis is an inflammatory heart disease and heart-specific autoimmunity plays an important role in development and progression of the disease. TNF-α is a potent pro-inflammatory cytokine implicated in pathogenesis in many inflammatory diseases. Unexpectedly, clinical studies showed that high dose anti-TNF-α therapy increased hospitalization and mortality of heart failure patients. Purpose To elucidate the role of TNF-α in heart-specific autoimmunity and in activation of cardiac microvascular endothelial cells in autoimmune response. Methods Experimental autoimmune myocarditis (EAM) was induced in BALB/c mice by immunization with α-myosin heavy chain peptide (α-MyHC) together with complete Freund's adjuvant. Development of myocarditis in the absence of adjuvant was analysed in TCR-M mice, which CD4+ T cells expressed transgenic T cell receptor recognizing α-MyHC. The role of TNF-α was addressed using haploinsufficient Tnf+/−, knockout Tnf−/− and TCR-M x Tnf+/− mice. Effects of antigen-dependent T cell response on cardiac microvascular endothelial cell (cMVEC) activation were assessed by flow cytometry, immunoblotting and leukocyte-endothelium adhesion assay. Inflammatory cells were phenotyped using flow cytometry, cytokine production was measured by ELISA. Results EAM induction resulted in reduced prevalence of myocarditis in Tnf+/− and Tnf−/− comparing wild-type mice at day 21 after disease induction. However, Tnf+/− and Tnf−/− mice that developed myocarditis showed higher severity of the disease than wild-type controls. On the other hand, TCR-M x Tnf+/− mice showed exacerbated myocarditis at age of 2 months and were characterized by increased mortality comparing with TCR-M controls. TCR-M Tnf+/− mice showed increased total number of cardiac infiltrates compared to TCR-M controls, but no difference in myeloid subsets were observed. In contrast, Tnf+/− and Tnf−/− mice showed significantly increased percentage of T effector cells in spleens and blood in both myocarditis models. Stimulation with rTNF-α induced expression of intercellular adhesion molecules (ICAM1, VCAM1 and P-selectin) on cMVECs, which was associated with increased ability to bind leukocytes under shear flow conditions. TNF-α deficiency had, however, no impact on antigen-specific activation and proliferation of T-cells. Medium conditioned of antigen-activated wild-type, Tnf+/− and Tnf−/− CD4+ T cells showed similar cMVEC activation measured by increased expression of intercellular adhesion molecules and binding of leukocytes under shear flow condition. Furthermore, Tnf+/− and Tnf−/m- myeloid cells showed increased production of IL-6. Conclusions Our data suggest that TNF-α protects the heart from excessive autoimmune reaction by suppressing expansion of autoreactive effector T cells. Thus, this study uncovers a cardioprotective role of proinflammatory TNF-α and potentially can explain the deleterious effect of high dose anti-TNF-α therapy in heart failure patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The National Science Centre Poland

scholarly journals Beneficial Effect of Dimethyl Fumarate on Experimental Autoimmune Uveitis is Dependent of Pro-Inflammatory Markers Immunomodulation

2021 ◽  
Author(s):  
Chafia TOUIL-BOUKOFFA ◽  
Moussa Labsi ◽  
Imene Soufli ◽  
Houda Belguendouz ◽  
Sara Djebbara ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Tap Water ◽  
Control Group ◽  
Histological Structure ◽  
Intragastric Administration ◽  
Autoimmune Uveitis ◽  
Experimental Autoimmune Uveoretinitis ◽  
Tnf Α ◽  
Experimental Autoimmune

Abstract Autoimmune uveitis is an inflammatory disease of the eye and is one of the major causes of blindness worldwide. Experimental autoimmune uveoretinitis (EAU) constitutes an animal disease model of human endogenous uveitis. In our study, we investigated the immunomodulatory effect of Dimethylfumarate (DMF) using bovine retinal extract-induced uveitis in a Female Wistar rats. To evaluate the in vivo efficacy, Female Wistar rats were divided into 7 experimental groups: control group (n = 5), consisting of non-immunized animals; Uveoretinitis (n = 5), and DMF/Uveoretinitis groups (n = 15), which received a subcutaneous injection of bovine retinal extract emulsified in complete Freund’s adjuvant; MC group (n = 5), treated by daily intragastric administration of methylcellulose 0.08% in tap water; DMF group, consisting of control positive group, rats received daily oral gavage administration of 500 µL of Dimethylfumarate at 100mg/Kg dissolved in 0.08% methylcellulose in tap water (n = 5). On days 14 post immunization, the rats were then euthanized and associated indications were investigated to evaluate the therapeutic efficacy. Nitric oxide (NO) and TNF-α were assessed in plasma. Meanwhile, eyes were collected for histological and immunohistochemical studies. The retinal expression of iNOS, CD68, CD20, CD25, CD4, and CD8 was examined. Interestingly, DMF enhanced a significant reduction of NO and TNF-α production in the treated group. This effect was strongly related to the histological structure of eyes improvement. In the same context, a significant decrease of iNOS, CD68, and CD20 expression and CD25 increase expression were reported in retinal tissue of DMF/Uveoretinitis group in comparison to the immunized group. Collectively, our results indicate that DMF treatment has a beneficial effect in experimental autoimmune uveoretinitis and could constitute a good candidate for monitoring an ocular inflammatory diseases.

scholarly journals تاثیر چهارهفته فعالیت هوازی بر نسبت سطوح سرمی عامل نکروز تومور آلفا، اینترلوکین-10 و میزان فاکتور نوروتروفیک مشتق‌ از مغز در بافت مغز موش های C57 از طریق القایExperimental Autoimmune Encephalomyelitis (EAE)

2018 ◽  
Author(s):  
اعظم جورابلو ◽  
عبدالمهدی نصیرزاده ◽  
سید مهدی سیدالحسینی ◽  
مریم وطن دوست
Keyword(s):  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Autoimmune Encephalomyelitis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Phosphate Buffered Saline ◽  
Necrosis Factor ◽  
Experimental Autoimmune

مقدمه:  هدف از این پژوهش بررسي اثربخشي 4 هفته تمرين هوازي شنا بر نسبت سطوح سرمی سایتوکاین­های Tumor Necrosis Factor alpha) TNF-α) و (Interleukin 10) IL-10 و میزان فاکتور نوروتروفیک مشتق از مغز (Brain Derived Neurotrophic Factor یا BDNF) در بافت مغز موش‌های مدل حیوانی مالتیپل‌اسکلروزیس از طریق القای (Experimental Autoimmune Encephalomyelitis یا EAE ) بود. روش بررسی: دراین مطالعه تجربی،80 سر موش سوری ماده با نژاد C57BL/6 با سن 12-10 هفته و وزن 2±20 گرم به 8 گروه 10 تایی (سالم کنترل، سالم شنا، MS کنترل، MS شنا، MS اینترفرون، MS اینترفرون و شنا، MS شاهد تزریق، MS شاهد شنا و تزریق) تقسیم شدند. جهت القای EAE، 300 میکروگرم MOG (35-55)  (Myelin Oligodendrocyte Glycoprotein)در حجم 100 میکرولیتر PBS (Phosphate buffered saline) و ادجوانت کامل (Complete Freund's Adjuvant)  مخلوط و به صورت زیر جلدی تزریق شد. هم زمان با تزريق اول و 48 ساعت بعد از آن، 300 نانوگرم سم سياه سرفه PT) یاtoxin Pertussis  ( به صورت داخل صفاقي تزريق شد. موش هاي مصرف كننده داروی اينترفرون بتا، از هفته اول پس از شروع درمان، روزانه به ميزان 150 واحد بين المللي/گرم از اين دارو را به صورت زير جلدي دريافت كردند. علايم باليني و وزن موش ها روزانه بررسي و ثبت شد. براي گروه هاي تمرين، روزانه 30 دقيقه به مدت 4 هفته، هفته اي 5 جلسه، فعاليت هوازي در محفظه شنا اجرا شد. در پایان پروتکل بافت مغز جداسازی و نمونه­های خونی از قلب استخراج شد و از روش (ELISA) Enzyme – linked immunosobent assay  براي اندازه گيري فاکتورهای مذکور استفاده گرديد. برای آنالیز داده­ها از نرم افزار SPSS(16) استفاده و سطح معني­داري آزمون­ها 05/0 در نظر گرفته شد. داده هاي به دست آمده، با استفاده از آزمون ANOVA way-One تجزيه و تحليل شد. نتایج: بر اساس يافته هاي اين مطالعه، ورزش نسبت به تیمار اينترفرون بتا - 1، به عنوان عامل مؤثرتري منجر به افزایش معنادار فاکتور BDNF در مغز موش‌ها، افزایش IL-10 و کاهش TNF-α در سرم شد. نتیجه‌گیری: تمرین هوازی شنا به احتمال زیاد می تواند از طریق کنترل عوامل التهابی به بازسازی میلین و یا کاهش سرعت تخریب میلین کمک می کند و و از این طریق، به بهبود بالینی بیماران مبتلا به MS منجر شود..

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