scholarly journals Anti-neutrophil properties of natural gingerols in models of lupus

JCI Insight ◽  
2020 ◽  
Author(s):  
Ramadan A. Ali ◽  
Alex A. Gandhi ◽  
Lipeng Dai ◽  
Julia K. Weiner ◽  
Shanea K. Estes ◽  
...  
Keyword(s):  
Models Of Lupus

scholarly journals VDAC1 in the diseased myocardium and the effect of VDAC1-interacting compound on atrial fibrosis induced by hyperaldosteronism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hadar Klapper-Goldstein ◽  
Ankit Verma ◽  
Sigal Elyagon ◽  
Roni Gillis ◽  
Michael Murninkas ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Apoptotic Cell ◽  
Anion Channel ◽  
Immunohistochemical Analysis ◽  
Voltage Dependent Anion Channel ◽  
Cardiac Tissues ◽  
Therapeutic Implications ◽  
Voltage Dependent ◽  
Models Of Lupus

AbstractThe voltage-dependent anion channel 1 (VDAC1) is a key player in mitochondrial function. VDAC1 serves as a gatekeeper mediating the fluxes of ions, nucleotides, and other metabolites across the outer mitochondrial membrane, as well as the release of apoptogenic proteins initiating apoptotic cell death. VBIT-4, a VDAC1 oligomerization inhibitor, was recently shown to prevent mitochondrial dysfunction and apoptosis, as validated in mouse models of lupus and type-2 diabetes. In the present study, we explored the expression of VDAC1 in the diseased myocardium of humans and rats. In addition, we evaluated the effect of VBIT-4 treatment on the atrial structural and electrical remodeling of rats exposed to excessive aldosterone levels. Immunohistochemical analysis of commercially available human cardiac tissues revealed marked overexpression of VDAC1 in post-myocardial infarction patients, as well as in patients with chronic ventricular dilatation\dysfunction. In agreement, rats exposed to myocardial infarction or to excessive aldosterone had a marked increase of VDAC1 in both ventricular and atrial tissues. Immunofluorescence staining indicated a punctuated appearance typical for mitochondrial-localized VDAC1. Finally, VBIT-4 treatment attenuated the atrial fibrotic load of rats exposed to excessive aldosterone without a notable effect on the susceptibility to atrial fibrillation episodes induced by burst pacing. Our results indicate that VDAC1 overexpression is associated with myocardial abnormalities in common pathological settings. Our data also indicate that inhibition of the VDAC1 can reduce excessive fibrosis in the atrial myocardium, a finding which may have important therapeutic implications. The exact mechanism\s of this beneficial effect need further studies.

scholarly journals No Evidence of Pathogenic Involvement of Cathelicidins in Patient Cohorts and Mouse Models of Lupus and Arthritis

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115474 ◽  
Author(s):  
D. Kienhöfer ◽  
J. Hahn ◽  
I. Schubert ◽  
C. Reinwald ◽  
N. Ipseiz ◽  
...  
Keyword(s):  
Mouse Models ◽  
Models Of Lupus

Genetics of Systemic Autoimmunity in Mouse Models of Lupus

2000 ◽  
Vol 19 (4-5) ◽  
pp. 367-387 ◽  
Author(s):  
Dwight H. Kono ◽  
Argyrios N. Theofilopouuos
Keyword(s):  
Mouse Models ◽  
Systemic Autoimmunity ◽  
Models Of Lupus

scholarly journals Overexpression of TLR7 promotes cell-intrinsic expansion and autoantibody production by transitional T1 B cells

2013 ◽  
Vol 210 (12) ◽  
pp. 2773-2789 ◽  
Author(s):  
Natalia V. Giltiay ◽  
Craig P. Chappell ◽  
Xizhang Sun ◽  
Nikita Kolhatkar ◽  
Thomas H. Teal ◽  
...  
Keyword(s):  
B Cells ◽  
Autoantibody Production ◽  
T1 Stage ◽  
Ligand Stimulation ◽  
High Concentrations ◽  
Rna Complexes ◽  
Models Of Lupus ◽  
Splenic Red Pulp

Toll-like receptor (TLR), a ligand for single-stranded RNA, has been implicated in the development of pathogenic anti-RNA autoantibodies both in systemic lupus erythematous (SLE) patients and in murine models of lupus. It is still unclear, however, where and how TLR7-mediated interactions affect the development of autoreactive B cells. We found that overexpression of TLR7 in transgenic mice (TLR7.1Tg) leads to marked alterations of transitional (T1) B cells, associated with their expansion and proliferation within the splenic red pulp (RP). This phenotype was intrinsic to the T1 subset of B cells and occurred independently of type 1 IFN signals. Overexpression of RNase in TLR7.1Tg mice significantly limited the expansion and proliferation of T1 cells, indicating that endogenous RNA complexes are driving their activation. TLR7.1Tg T1 cells were hyper-responsive to anti-IgM and TLR7 ligand stimulation in vitro and produced high concentrations of class-switched IgG2b and IgG2c, including anti-RNA antibodies. Our results demonstrate that initial TLR7 stimulation of B cells occurs at the T1 stage of differentiation in the splenic RP and suggest that dysregulation of TLR7 expression in T1 cells can result in production of autoantibodies.

scholarly journals Metformin improves FOXP3 mRNA expression through suppression of interferon gamma levels in pristane-induced murine models of lupus

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 342
Author(s):  
Stevent Sumantri ◽  
Mochammad Hatta ◽  
Rosdiana Natzir ◽  
Haerani Rasyid ◽  
Iris Rengganis ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Lupus Erythematosus ◽  
Pearson Correlation ◽  
Fold Change ◽  
Mean Difference ◽  
Saline Control ◽  
Foxp3 Mrna ◽  
Treatment Groups ◽  
Metformin Group ◽  
Models Of Lupus

Background:  A recent study has indicated the potential of metformin therapy for lupus in animal models, but there has been no study evaluating the effect on pristane-induced lupus. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristane-induced female BALB/c mice. Methods: In total, 31 female BALB/c mice, aged 6 weeks, were intraperitoneally induced with 0.5 ml of pristane (2,6,10,14-tetramethylpentadecane). After 120 days, the mice were grouped and treated with various treatments: normal saline 100 mcl, oral metformin 100mg/kgBW, or intraperitoneal metformin 100mg/kgBW. After 60 days of treatment, all treatment groups were sacrificed, and kidney specimens prepared and stained using hematoxylin and esosin. Results: IFNγ levels of saline controls vs. oral metformin group was 309.39 vs. 292.83 pg/mL (mean difference 16.56 pg/mL; 95% CI 0.74-32.37; p=0.042), and saline control vs. intraperitoneal metformin group was 309.39 vs. 266.90 pg/mL (mean difference 42.49 pg/mL; 95% CI 29.24-55.73 pg/mL; p<0.004). FOXP3 mRNA expression changes in saline controls vs. oral metformin group was 6.90 vs. 7.79-fold change (mean difference -0.89-fold change; 95% CI -1.68-(-0.11); p=0.03)  and in saline controls vs. intraperitoneal metformin group was 6.90 vs. 9.02-fold change (mean difference -2.12-fold change; 95% CI -2.99-(-1.25); p=<0.001). Correlation analysis of FOXP3 mRNA expression and IFNγ level changes revealed a Pearson correlation of -0.785 (p=0.001) and R2 value of 0.616 (p=0.001). Conclusion: Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus. Intraperitoneal metformin, i.e intravenous administration in human, could provide a novel route of administration to improve the effect of metformin for lupus patients.

scholarly journals Niclosamide Suppresses the Expansion of Follicular Helper T Cells and Alleviates Disease Severity in Two Murine Models of Lupus via STAT3

2020 ◽  
Author(s):  
Se Gwang Jang ◽  
Jaeseon Lee ◽  
Seung-Min Hong ◽  
Young-Seok Song ◽  
Min Jun Kim ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Plasma Cells ◽  
Immune Cell ◽  
Parasitic Infections ◽  
Therapeutic Effects ◽  
Murine Models ◽  
Autoantibody Production ◽  
Follicular Helper ◽  
Dsdna Antibody ◽  
Models Of Lupus

Abstract Background. Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (TFH) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to TFH cells. Niclosamide is an anti-helminthic drug used to treat parasitic infections but also exhibits a therapeutic effect on autoimmune diseases due to its potential immune regulatory effects. In this study, we examined whether Niclosamide treatment could relieve lupus-like autoimmunity by modulating the differentiation of TFH cells in two murine models of lupus.Methods. 10-week-old MRL/lpr mice were orally administered with 100 mg/kg of Niclosamide or with 0.5% methylcellulose (MC, vehicle) daily for 7 weeks. TLR7 agonist, resiquimod was topically applied to an ear of 8-week-old C57BL/6 mice 3 times a week for 5 weeks. And they were orally administered with 100 mg/kg of Niclosamide or with 0.5% MC daily for 5 weeks. Every mouse was analyzed for lupus nephritis, proteinuria, autoantibodies, immune complex, immune cell subsets at the time of the euthanization.Results. Niclosamide treatment greatly improved proteinuria, anti-dsDNA antibody levels, immunoglobulin subclass titers, histology of lupus nephritis, and C3 deposition in MRL/lpr and R848-induced mice. In addition, Niclosamide inhibited the proportion of TFH cells and PCs in the spleens of these animals, and effectively suppressed differentiation of TFH-like cells and expression of associated genes in vitro.Conclusions. Niclosamide exerted therapeutic effects on murine lupus models by suppressing TFH cells and plasma cells through STAT3 inhibition.

scholarly journals Mouse models of lupus: what they tell us and what they don’t

2018 ◽  
Vol 5 (1) ◽  
pp. e000199 ◽  
Author(s):  
Mara Lennard Richard ◽  
Gary Gilkeson
Keyword(s):  
Mouse Models ◽  
Models Of Lupus

scholarly journals Leaky-gut enhanced lupus progression in the Fc gamma receptor-IIb deficient and pristane-induced mouse models of lupus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arthid Thim-uam ◽  
Saowapha Surawut ◽  
Jiraphorn Issara-Amphorn ◽  
Thiranut Jaroonwitchawan ◽  
Pratsanee Hiengrach ◽  
...  
Keyword(s):  
Mouse Models ◽  
Leaky Gut ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Models Of Lupus
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