Interleukin-12 exacerbates symptoms in an MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus

Exp Ther Med. 2021 Jun;21(6):627. doi: 10.3892/etm.2021.10059. Epub 2021 Apr 15.ABSTRACTInterleukin (IL)-12 modulates the generation and function of a variety of immune cells and serves an important role in the pathogenesis of autoimmune diseases. However, the precise role of IL-12 in the pathogenesis of systemic lupus erythematosus (SLE) remains to be elucidated. In the present study, the serum levels of IL-12 in patients with SLE were determined using an ELISA. The association between serum levels of IL-12 and clinical and laboratory indices, specifically, disease activity and complement 3, were analyzed. Recombinant IL-12 or an anti-IL-12 antibody was used to treat the MRL/MpJ-Faslpr mouse model of systemic lupus erythematosus. The glomerulonephritis and inflammatory cell infiltration was examined to evaluate histological changes using hematoxylin and eosin and Periodic acid-Schiff staining. Serum creatinine and proteinuria were used to determine renal function. The levels of anti-double stranded DNA and anti-nuclear autoantibodies were assessed. The results demonstrated that serum levels of IL-12 were markedly increased in patients with SLE compared with controls and in lupus model mice in comparison with control mice. The serum levels of IL-12 increased with disease severity in patients with SLE. SLE-like symptoms were exacerbated in lupus model mice treated with exogenous IL-12. However, SLE-like symptoms were ameliorated in lupus model mice treated with an anti-IL-12 a...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Authors: Source Type: research

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Abstract The kidney is frequently involved by autoimmune rheumatic diseases. The renal manifestations may be variable, ranging from asymptomatic proteinuria and microscopic haematuria to nephrotic syndrome and rapidly progressive glomerulonephritis or vasculitis. In a number of cases the kidney involvement is related to the treatment of the original disease and may represent a major cause of morbidity and mortality. Thus, it is important for nephrologists and rheumatologists to remember that dysfunction of the kidney may be part of the primary systemic disorder or consequence of its pharmacotherapy. In the first p...
Source: Journal of Nephrology - Category: Urology & Nephrology Authors: Tags: J Nephrol Source Type: research
This study was undertaken to test the hypothesis that inhibition of Pim‐1 would have therapeutic potential in patients with LN.MethodsPim ‐1 expression was analyzed in lupus‐prone (NZB × NZW)F1 mice (n = 6), human peripheral blood mononuclear cells (PBMCs) from SLE patients (n = 10), and glomeruli from patients with LN (n = 8). The therapeutic effect of the Pim‐1 inhibitor AZD1208 was assessed in the same murine lupus model (n = 10 mice per group). In vitro analysis was conducted to explore the mechanisms of action of Pim‐1 in mouse and human podocytes after Pim‐1 expression had been induced by anti&ndash...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Original Article Source Type: research
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Grouping HK-...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: Our data indicate reduced P2X7R expression and function in SLE patients compared with HC and, conversely, increased IL-6 signaling. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 as a possible therapeutic target especially in lupus serositis. Introduction With the first reports of Burnstock in 1970s, adenosine triphosphate (ATP) has passed from a simple molecule devoted to energy reserve, to a relevant extracellular signaling molecule able to mediate numerous physiological and pat...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractObjectiveLupus nephritis (LN) is a major determinant of morbidity and mortality in systemic lupus erythematosus (SLE). Pim ‐1 regulates lymphocyte proliferation and activation. The role of Pim‐1 in autoimmune disease remains unclear. Therefore, we hypothesize that Pim‐1 inhibition would have therapeutic potential for LN.MethodsWe first analyzed Pim ‐1 expression in lupus‐prone NZB/W F1 mice (n=6), in human peripheral blood mononuclear cells (PBMCs) of SLE patients (n=10), and in the glomeruli of LN patients (n=8). The therapeutic effect of Pim‐1 inhibitor AZD1208 was assessed in this lupus model (n=10/g...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Full Length Source Type: research
Purpose of review Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus and is characterized by proteinuria and renal failure. Proteinuria is a marker of poor prognosis and is attributed to podocyte loss and dysfunction. It is often debated whether these cells are innocent bystanders or active participants in the pathogenesis of glomerulonephritis. Recent findings Podocytes share many elements of the innate and adaptive immune system. Specifically, they produce and express complement components and receptors which when dysregulated appear to contribute to podocyte damage and LN. In parallel, ...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: IMMUNOPATHOGENESIS AND TREATMENT OF AUTOIMMUNE DISEASES: Edited by George C. Tsokos Source Type: research
ConclusionGalectin‐9 is required for the induction and development of lupus nephritis and arthritis in pristane‐induced mice model of SLE. The current investigation provided a new strategy, in which the antagonism of Galectin‐9 is beneficial for the treatment of nephritis and arthritis in SLE by targeting activated macrophages.This article is protected by copyright. All rights reserved.
Source: Arthritis and Rheumatism - Category: Rheumatology Authors: Tags: Full Length Source Type: research
(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcγ receptor signaling. Acta Pharmacol Sin. 2017 Sep 07;: Authors: Qi Q, Li H, Lin ZM, Yang XQ, Zhu FH, Liu YT, Shao MJ, Zhang LY, Xu YS, Yan YX, Sun LL, He SJ, Tang W, Zuo JP Abstract (5R)-5-hydroxytriptolide (LLDT-8) is a novel triptolide analog that has been identified as a promising candidate for treating autoimmune diseases and has been shown to be effective in treating murine collagen-induced arthritis and lupus nephritis. In the present study, we investigated the therapeutic...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by development of autoantibodies to nuclear and cytoplasmic antigens. A small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative antinuclear antibody tests. Our report describes a 5-year-old male who presented with histopathological findings suggestive of lupus nephritis with no clinical signs or symptoms of SLE and negative autoantibodies. He was treated with corticosteroids, mycophenolate mofetil, and monthly intravenous cyclophosphamide. During the 2-year follow-up period, the proteinuria...
Source: Case Reports in Nephrology and Dialysis - Category: Urology & Nephrology Source Type: research
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