Therapeutic potential of DCB-SLE1, an extract of a mixture of Chinese medicinal herbs, for severe lupus nephritis

2011 ◽  
Vol 301 (4) ◽  
pp. F751-F764 ◽  
Author(s):  
Pei-Yi Tsai ◽  
Shuk-Man Ka ◽  
Jia-Ming Chang ◽  
Wen-Liang Chang ◽  
Yuan-Jen Huang ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
B Cell ◽  
Cell Activation ◽  
Acute Onset ◽  
Medicinal Herbs ◽  
Autoimmune Response ◽  
Therapeutic Effects ◽  
Chinese Medicinal Herbs ◽  
Autoantibody Production ◽  
Severe Lupus Nephritis

The pathogenesis of lupus nephritis is mainly attributable to a complex interaction between the innate and adaptive immune systems, including T and B cell function abnormalities. In addition to autoantibody production and immune complex deposition, Th1 and Th17 cytokines may play key roles in the development and progression of lupus nephritis. Acute onset of severe lupus nephritis remains a challenge in terms of prevention and treatment. In the present study, we evaluated the therapeutic effects of DCB-SLE1, an extract of a mixture of four traditional Chinese medicinal herbs ( Atractylodis macrocephalae Rhizoma, Eucommiae cortex , Lonicerae caulis , and Hedyotidis diffusae Herba), on an accelerated severe lupus nephritis model, characterized by acute onset of proteinuria, azotemia, autoantibody production, and development of severe nephritis, induced by twice weekly injection of New Zealand black/white F1 mice with Salmonella -type lipopolysaccharide. DCB-SLE1 was administered daily by gavage starting 2 days after the first dose of induction of lipopolysaccharide, and the mice were euthanized at week 1 or week 5. The results showed that DCB-SLE1 significantly ameliorated the hematuria, proteinuria, renal dysfunction, and severe renal lesions by 1) suppression of B cell activation and decreased autoantibody production; 2) negative regulation of T cell activation/proliferation and natural killer cell activity; 3) suppression of IL-18, IL-6, and IL-17 production and blocking of NF-κB activation in the kidney; and 4) prevention of lymphoid and renal apoptosis. These results show that DCB-SLE1 can protect the kidney from autoimmune response-mediated acute and severe damage through systemic immune modulation and anti-inflammation pathways.

Mercury induces polyclonal B cell activation, autoantibody production and renal immune complex deposits in young (NZB × NZW)F1 hybrids

1996 ◽  
Vol 26 (7) ◽  
pp. 1519-1526 ◽  
Author(s):  
Sanad Al-Balaghi ◽  
Erna Möller ◽  
Göran Möller ◽  
Manuchehr Abedi-Valugerdi
Keyword(s):  
B Cell ◽  
Immune Complex ◽  
Cell Activation ◽  
F1 Hybrids ◽  
B Cell Activation ◽  
Autoantibody Production

SuO006DELETION OF SMAD3 WORSONS LUPUS NEPHRITIS BY PROMOTING B CELL ACTIVATION VIA E4BP4-MINCLE-SYK MECHANISM

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Jinhong Li ◽  
Yang Hui ◽  
Tang Mk Patrick ◽  
Zhu Wenjian ◽  
Huang Xiaoru ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation

Expression of XBP1s in B lymphocytes is critical for pristane-induced lupus nephritis in mice

2020 ◽  
Vol 318 (5) ◽  
pp. F1258-F1270 ◽  
Author(s):  
Li Xiang ◽  
An Liu ◽  
Guoshuang Xu
Keyword(s):  
B Cells ◽  
Lupus Nephritis ◽  
Mouse Model ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
B Lymphocyte ◽  
B Cell Activation ◽  
Protein Levels ◽  
Almost All

B lymphocyte hyperactivity plays a pathogenic role in systemic lupus erythematosus (SLE), and spliced X box-binding protein 1 (XBP1s) has been implicated in B cell maturation and differentiation. We hypothesized that blockade of the XBP1s pathway inhibits the B cell hyperactivity underlying SLE and lupus nephritis (LN) development. In the present study, we systematically evaluated the changes in B cell activation induced by the Xbp1 splicing inhibitor STF083010 in a pristane-induced lupus mouse model. The lupus mouse model was successfully established, as indicated by the presence of LN with markedly increased urine protein levels, renal deposition of Ig, and mesangial cell proliferation. In lupus mice, B cell hyperactivity was confirmed by increased CD40 and B cell-activating factor levels. B cell activation and plasma cell overproduction were determined by increases in CD40-positive and CD138-positive cells in the spleens of lupus mice by flow cytometry and further confirmed by CD45R and Ig light chain staining in the splenic tissues of lupus mice. mRNA and protein expression of XBP1s in B cells was assessed by real-time PCR, Western blot analysis, and immunofluorescence analysis and was increased in lupus mice. In addition, almost all changes were reversed by STF083010 treatment. However, the expression of XBP1s in the kidneys did not change when mice were exposed to pristane and STF083010. Taken together, these findings suggest that expression of XBP1s in B cells plays key roles in SLE and LN development. Blockade of the XBP1s pathway may be a potential strategy for SLE and LN treatment.

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 CXCL13 as biomarker for histological involvement in Sjögren’s syndrome

Rheumatology ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 165-170 ◽  
Author(s):  
Serena Colafrancesco ◽  
Roberta Priori ◽  
Charlotte G Smith ◽  
Antonina Minniti ◽  
Valentina Iannizzotto ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Severity ◽  
Cell Activation ◽  
Serum Levels ◽  
Serum Marker ◽  
Queen Elizabeth Hospital ◽  
B Cell Activation ◽  
Autoantibody Production ◽  
Germinal Centres ◽  
University Of Rome

Abstract Objectives SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres’ formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres’ activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects’ (n = 19) sera were used as control. Results CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. Conclusion Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice

2020 ◽  
Vol 98 (2) ◽  
pp. 378-390 ◽  
Author(s):  
Shin-Ruen Yang ◽  
Kuo-Feng Hua ◽  
Lichieh Julie Chu ◽  
Yeu-Kuang Hwu ◽  
Shun-Min Yang ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Nlrp3 Inflammasome ◽  
Acute Onset ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Severe Lupus Nephritis

scholarly journals Active Inhibition of Plasma Cell Development in Resting B Cells by Microphthalmia-associated Transcription Factor

2004 ◽  
Vol 200 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Ling Lin ◽  
Andrea J. Gerth ◽  
Stanford L. Peng
Keyword(s):  
Transcription Factor ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Cell Activation ◽  
Terminal Differentiation ◽  
B Cell Activation ◽  
Autoantibody Production ◽  
B Cell Homeostasis ◽  
Antibody Secretion

B cell terminal differentiation involves development into an antibody-secreting plasma cell, reflecting the concerted activation of proplasma cell transcriptional regulators, such as Blimp-1, IRF-4, and Xbp-1. Here, we show that the microphthalmia-associated transcription factor (Mitf) is highly expressed in naive B cells, where it antagonizes the process of terminal differentiation through the repression of IRF-4. Defective Mitf activity results in spontaneous B cell activation, antibody secretion, and autoantibody production. Conversely, ectopic Mitf expression suppresses the expression of IRF-4, the plasma cell marker CD138, and antibody secretion. Thus, Mitf regulates B cell homeostasis by suppressing the antibody-secreting fate.

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