AB0221 Estrogen modulation of endosome-associated toll-like receptors and ZAS3: An underlying mechanism of gender-BIAS in systemic lupus erythematosus?

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 650.4-650
Author(s):  
N. Young ◽  
A. Friedman ◽  
B. Kaffenberger ◽  
H. James ◽  
L.-C. Wu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Gender Bias ◽  
Lupus Erythematosus ◽  
Underlying Mechanism ◽  
Toll Like Receptors ◽  
Systemic Lupus

Expression of Toll-like receptors 2 and 4 in the saliva of patients with systemic lupus erythematosus and chronic periodontitis

2021 ◽  
Author(s):  
Consuelo P. C. Marques ◽  
Vandilson P. Rodrigues ◽  
Larissa C. de Carvalho ◽  
Louise P. Nichilatti ◽  
Mayra M. Franco ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Chronic Periodontitis ◽  
Toll Like Receptors ◽  
Systemic Lupus

scholarly journals Eryptosis as an Underlying Mechanism in Systemic Lupus Erythematosus-Related Anemia

2016 ◽  
Vol 40 (6) ◽  
pp. 1391-1400 ◽  
Author(s):  
Peipei Jiang ◽  
Maohong Bian ◽  
Wenjuan Ma ◽  
Chunqiu Liu ◽  
Peng Yang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Healthy Volunteers ◽  
Lupus Erythematosus ◽  
Calcium Ion ◽  
Underlying Mechanism ◽  
Cytosolic Calcium ◽  
Systemic Lupus ◽  
Cell Shrinkage ◽  
Experimental Subjects ◽  
Underlying Mechanisms

Background: The progression of systemic lupus erythematosus (SLE) leads to anemia in patients, adversely affecting prognosis. The diverse causes of anemia may include excessive eryptosis or premature suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine (PS) exposure on the cell surface. The present study explored if SLE enhances eryptosis and the underlying mechanisms. Materials and Methods: Eryptosis was assessed using flow cytometry in healthy volunteers (n = 20) and anemic patients hospitalized for SLE (n = 22), for parameters including PS exposure, cell volume, cytosolic calcium ion (Ca2+) levels and reactive oxygen species (ROS) and ceramide abundance. These indicators were measured in erythrocytes of experimental subjects and erythrocytes treated with plasma from healthy volunteers or SLE patients. Results: The hemoglobin and hematocrit levels were significantly lower in anemic SLE patients than in healthy volunteers (***p<0.001, p<0.001, respectively). The percentage of PS-exposing erythrocytes was significantly higher in SLE patients than in healthy volunteers (p<0.001), accompanied by an increase in cytosolic Ca2+ levels, oxidative stress. The measurements of PS and Ca2+ levels were significantly higher in the erythrocytes of healthy volunteers following incubation in plasma of SLE patients than in plasma of healthy volunteers for 24h (***p<0.001, *p<0.05 respectively). Conclusion: Eryptosis is enhanced in SLE and may contribute to anemia. The probable underlying mechanisms may be an excessive formation of ROS in erythrocytes. Also, some plasma components may trigger eryptosis by increasing the cytosolic Ca2+ concentration.

scholarly journals Interferon Regulatory Factor 5 in the Pathogenesis of Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Candace M. Cham ◽  
Kichul Ko ◽  
Timothy B. Niewold
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Interferon Regulatory Factor ◽  
Immune Defense ◽  
Toll Like Receptors ◽  
Regulatory Factor ◽  
Systemic Lupus ◽  
Interferon Regulatory Factor 5

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple genetic risk factors, high levels of interferon alpha (IFN-α), and the production of autoantibodies against components of the cell nucleus. Interferon regulatory factor 5 (IRF5) is a transcription factor which induces the transcription of IFN-αand other cytokines, and genetic variants of IRF5 have been strongly linked to SLE pathogenesis. IRF5 functions downstream of Toll-like receptors and other microbial pattern-recognition receptors, and immune complexes made up of SLE-associated autoantibodies seem to function as a chronic endogenous stimulus to this pathway. In this paper, we discuss the physiologic role of IRF5 in immune defense and the ways in whichIRF5variants may contribute to the pathogenesis of human SLE. Recent data regarding the role ofIRF5in both serologic autoimmunity and the overproduction of IFN-αin human SLE are summarized. These data support a model in which SLE-risk variants of IRF5 participate in a “feed-forward” mechanism, predisposing to SLE-associated autoantibody formation, and subsequently facilitating IFN-αproduction downstream of Toll-like receptors stimulated by immune complexes composed of these autoantibodies.

scholarly journals Artemisinin derivative SM934, influences the activation, proliferation, differentiation and antibody-secreting capacity of β-cells in systemic lupus erythematosus mice via inhibition of TLR7/9 signaling pathway

2021 ◽  
Vol 18 (7) ◽  
pp. 1391-1396
Author(s):  
Yajuan Li ◽  
Lixin Zhao ◽  
Xuehui Yang ◽  
Jing Chen ◽  
Wenjing Xu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
B Lymphocyte ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Artemisinin Derivative ◽  
Systemic Lupus ◽  
Dose Dependent

Purpose: To study the influence of artemisinin derivative, SM934 on activation, proliferation, differentiation and antibody-secreting capacity of B cells of systemic lupus erythematosus (SLE) mice, and the underlying mechanism. Methods: Female MRL/lpr mice (n = 60) were randomly assigned to four groups of 15 mice each: SLE, 2.5 mg/kg SM934; 5 mg/kg SM934, and 10 mg/kg SM934 groups. Serum levels of interleukins 6, 10, 17 and 21 (IL-6, IL-17, IL-10 and IL-21) were determined. The secretions of immunoglobulins G and M (IgG and IgM) by B cells were determined. The population of B lymphocyte subtypes was determined flow cytometrically. The expressions of Blimp-1 and Bcl-6, Toll-like receptors 7 and 9 (TLR7 and TLR9) mRNAs were determined. Results: SLE-induced upregulation of serum IL-10, IL-6, IL-17 and IL-21 was significantly and dosedependently reduced following a 2-month treatment with SM934 (p < 0.01). Treatment with SM934 significantly and dose-dependently accentuated B cell germinal center B cell populations, but significantly and dose-dependently decreased the populations of plasma and activated B cells (p < 0.01). The splenic levels of IgG and IgM were decreased in a dose-dependent fashion after 8 weeks of treatment (p < 0.01). Artemisinin derivative SM934 decreased the expression of Blimp-1, and upregulated the expression of Bcl-6, both in a dose-dependent manner (p < 0.01). Moreover, SM934 decreased the mRNA expressions of TLR7 and TLR9 in a dose-based manner (p < 0.01). Conclusion: Artemisinin derivative SM934 mitigates LSE syndromes by suppressing the TLR-induced B-cell stimulation and plasma cell generation

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