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Hansjoachim Anders - One of the best experts on this subject based on the ideXlab platform.
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2019 update of the joint european league against rheumatism and european renal association european dialysis and transplant association eular era edta recommendations for the management of lupus Nephritis
Annals of the Rheumatic Diseases, 2020Co-Authors: Antonis Fanouriakis, Hansjoachim Anders, Myrto Kostopoulou, Kim Cheema, Martin Aringer, Ingeborg M Bajema, J Boletis, Eleni Frangou, Frederic HoussiauAbstract:Objective To update the 2012 EULAR/ERA–EDTA recommendations for the management of lupus Nephritis (LN). Methods Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. Results The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria 1 g/24 hours despite renin–angiotensin–aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. Conclusions We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.
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activation of toll like receptor 9 induces progression of renal disease in mrl fas lpr mice
The FASEB Journal, 2004Co-Authors: Hansjoachim Anders, Matthias Kretzler, Volker Vielhauer, Vaclav Eis, Yvonne Linde, Guillermo Perez De Lema, Frank Strutz, Stefan Bauer, Mark Rutz, Hermann WagnerAbstract:How bacterial or viral infections trigger flares of autoimmunity is poorly understood. As toll-like receptor (TLR)-9 activation by exogenous or endogenous CpG-DNA may contribute to disease activity of systemic lupus erythematosus, we examined the effects of CpG-oligodeoxynucleotides (ODN) or DNA derived from Escherichia coli (E. coli) on the course of Nephritis in MRL(lpr/lpr) mice. In kidneys of these mice, TLR9 localized to glomerular, tubulointerstitial, and perivascular infiltrates. After intraperitoneal injection labeled CpG-ODN localized to glomerular and interstitial macrophages and dendritic cells in nephritic kidneys of MRL(lpr/lpr) mice but not in healthy MRL controls. Furthermore, murine J774 macrophages and splenocytes from MRL(lpr/lpr) mice, but not tubular epithelial cells, renal fibroblasts, or mesangial cells, expressed TLR9 and up-regulated CCL5/RANTES mRNA upon stimulation with CpG-ODN in vitro. In vivo both E. coli DNA and CpG-ODN increased serum DNA autoantibodies of the IgG2a isotype in MRL(lpr/lpr) mice. This was associated with progression of mild to crescentic glomeruloNephritis, interstitial fibrosis, and heavy proteinuria. CpG-ODN increased renal CCL2/MCP-1 and CCL5/RANTES expression associated with increased glomerular and interstitial leukocyte recruitment. In contrast control GpC-ODN had no effect. We conclude that TLR9 activation triggers disease activity of systemic autoimmunity, for example, lupus Nephritis, and that adaptive and innate immune mechanisms contribute to the CpG-DNA-induced progression of lupus Nephritis.
Yoshio Suzuki - One of the best experts on this subject based on the ideXlab platform.
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protective effect of prostaglandin ep4 receptor agonist on anti glomerular basement membrane antibody associated Nephritis
Journal of Pharmacological Sciences, 2006Co-Authors: Tadashi Nagamatsu, Hirohito Imai, Michiyo Yokoi, Tsutomu Nishiyama, Yasushi Hirasawa, Toshiyuki Nagao, Yoshio SuzukiAbstract:Prostaglandin E(2)-receptor subtypes, EP(1), EP(2), EP(3), and EP(4), are present in the kidney. The aim of this study was to elucidate the anti-nephritic effect of an EP(4)-receptor agonist on an experimental nephritic model. Mice were injected i.v. with anti-glomerulus antiserum to induce Nephritis. Nephritic glomeruli generated more prostaglandin E(2) (2.6 and 0.7 ng) and less cyclic AMP than normal glomeruli (11 and 26 pmol). The production of cyclic AMP in nephritic glomeruli increased 67% in response to AE1-329, an EP(4) agonist, at 10(-5) M. Nephritic glomeruli expressed a lesser amount of mRNA of prostaglandin E(2)-receptor subtypes as compared with normal glomeruli. AE1-329 was administered s.c. at 100 microg/kg per day for 3 weeks. AE1-329 suppressed the increase in creatinine and cholesterol compared to those in the control nephritic mice. AE1-329-treated nephritic mice had less crescentic glomeruli and less deposition of rabbit IgG (anti-glomerular basement membrane antibody) in glomeruli than the control mice. AE1-329 prevented the development of glomeruloNephritis. These findings suggest that EP(4)-receptor agonists are a promising drug to prevent the development of glomeruloNephritis.
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modulation of anti glomerular basement membrane Nephritis in rats by ono 1301 a non prostanoid prostaglandin i2 mimetic compound with inhibitory activity against thromboxane a2 synthase
Japanese Journal of Pharmacology, 1997Co-Authors: Kazumi Hayashi, Tadashi Nagamatsu, Tatsuya Oka, Yoshio SuzukiAbstract:The antinephritic effects of ONO-1301 ([7,8-dihydro-5-[(E)-[[a-(3-pyridyl)benzylidene]-aminooxy]ethyl]-1 -naphtyloxy]acetic acid) on crescentic-type anti-glomerular basement membrane (GBM) Nephritis in rats were investigated. ONO-1301 was orally given to crescentic-type anti-GBM nephritic rats for 40 days after the induction of Nephritis. ONO-1301 (30 mg/kg) suppressed the elevation of protein excretion into urine. In the ONO-1301-treated rats, cholesterol and urea nitrogen content in the plasma was lower than that of the nephritic control rats. Histological observation demonstrated that ONO-1301 suppressed the incidence of crescent formation and adhesion of capillary wall to Bowman's capsule. However, ONO-1301 failed to inhibit the antibody production against rabbit IgG and the rat-IgG deposition on the GBM. The increase in very late antigen-4 (CD49b, VLA-4)-positive cells in nephritic glomeruli was significantly reduced by ONO-1301 treatment on day 5. cAMP-elevating agents inhibited the up-regulation of vascular cell adhesion molecule-1 (VCAM-1) expression on the surface of human umbilical vein endothelial cells (HUVECs) mediated by tumor necrosis factor (TNF)-alpha. These findings suggest that the antinephritic action of ONO-1301 is due to, at least in part, inhibition of intraglomerular accumulation of leukocytes through the prevention of the up-regulation of VCAM-1.
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Effect of DP-1904, a thromboxane A2 synthase inhibitor, on passive Heymann Nephritis in rats.
European journal of pharmacology, 1996Co-Authors: Toshiyuki Nagao, Tadashi Nagamatsu, Yoshio SuzukiAbstract:Abstract The antinephritic effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride], a thromboxane A2 synthase inhibitor, was evaluated using an experimental model of membranous nephropathy, viz. accelerated passive Heymann Nephritis in which the glomerular injury is mediated by immune complexes. DP-1904 markedly inhibited the development of glomerular alteration as well as the elevation of proteinuria and plasma creatinine. When the treatment was started from the 22nd day, at which time proteinuria is fully developed, DP-1904 showed beneficial effects on proteinuria and glomerular histopathological changes. DP-1904 apparently decreased the deposition of both rabbit immunoglobulin G and rat immunoglobulin G on glomerular basement membrane in nephritic rats. A single administration of DP-1904 restored the decreased renal tissue blood flow, inhibited glomerular thromboxane B2 production and increased glomerular prostaglandin E2 and 6-keto prostaglandin F1α production in nephritic rats. These results suggest that DP-1904 may be an effective agent for the treatment of idiopathic membranous nephropathy and that the beneficial effect of this drug may be due to the elimination of glomerular immune deposits and to an increase in renal tissue blood flow related to amelioration of the abnormal metabolism of arachidonic acid.
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acteoside a component of stachys sieboldii miq may be a promising antinephritic agent 3 effect of acteoside on expression of intercellular adhesion molecule 1 in experimental nephritic glomeruli in rats and cultured endothelial cells
Japanese Journal of Pharmacology, 1996Co-Authors: Kazumi Hayashi, Tadashi Nagamatsu, Mikio Ito, Hideo Yagita, Yoshio SuzukiAbstract:Abstract. It is known that adhesion molecules play a crucial role in the development of glomerulo-Nephritis. Therefore, we investigated the effects of acteoside on the expression of intercellular adhesion molecule-1 (ICAM-1) in nephritic glomeruli, in vivo, and human umbilical vein endothelial cells (HUVECs) and rat mesangial cells, in vitro. Acteoside treatment significantly decreased the up-regulation of ICAM-1 expression in nephritic glomeruli. Acteoside prevented the up-regulation of ICAM-1 expression mediated by inflammatory cytokines or phorbol 12-myristate 13-acetate on HUVECs and rat mesangial cells. Adhesion of neutrophils and macrophages to acteoside-treated HUVECs was suppressed to one half of that in untreated HUVECs. These data support the finding that acteoside inhibits the up-regulation of ICAM-1 in the nephritic glomeruli. Additionally, it is suggested that the antinephritic action of acteoside is due to the inhibition of intraglomerular accumulation of leukocytes through the prevention of the upregulation of ICAM-1. This is the first paper demonstrating that the up-regulation of ICAM-1 in nephritic glomeruli is inhibited by a natural product, acteoside.
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Suppression of experimental crescentic-type anti-glomerular basement membrane (GBM) Nephritis by FK506 (tacrolimus hydrate) in rats.
Japanese journal of pharmacology, 1996Co-Authors: Kazumi Hayashi, Tadashi Nagamatsu, Mikio Ito, Yoshio SuzukiAbstract:Abstract. The effect of FK506 (tacrolims hydrate), an immunosuppressive agent produced by Streptomyces tsukubaensis, on crescentic-type anti-glomerular basement membrane (GBM) Nephritis in rats was investigated. When rats were treated with FK506 from 1 or 20 days after the anti-GBM serum injection, FK506 inhibited the increase in urinary protein excretion. Histological observation demonstrated that FK506 suppressed glomerular alterations. In the FK506-treated rats, antibody production and rat-IgG and C3 deposits on the GBM were significantly less than those in the nephritic control group. FK506 treatment suppressed the accumulation of ED-l-positive cells, CD4-positive cells, CD8-positive cells, interleukin-2 (IL-2)-receptor-positive cells, leukocyte-function-associated antigen-1 (LFA-l)-positive cells and intercellular adhesion molecule-1 (ICAM-l)-expression in nephritic glomeruli. However, in the in vitro study, FK506 failed to inhibit the up-regulated ICAM-1 expression on endothelial cells in response to tumor necrosis factor (TNF)-α. On the other hand, IL-2 production from the spleen cells isolated from nephritic rats treated with FK506 was lower than that in the nephritic control rats. These results suggest that FK506 is effective against crescentic-type anti-GBM Nephritis and that the antinephritic mechanisms of FK506 is due to the inhibition of intraglomerular accumulation and activation of leukocytes through the suppression of ICAM-1 expression and IL-2 production.
Hermann Josef Grone - One of the best experts on this subject based on the ideXlab platform.
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bacterial lipopeptide triggers massive albuminuria in murine lupus Nephritis by activating toll like receptor 2 at the glomerular filtration barrier
Immunology, 2009Co-Authors: Rahul D Pawar, Liliana Castrezanalopez, Ramanjaneyulu Allam, Onkar P Kulkarni, Stephan Segerer, Ewa Radomska, Tobias N Meyer, Catherine Schwesinger, Nese Akis, Hermann Josef GroneAbstract:What are the molecular mechanisms of bacterial infections triggering or modulating lupus Nephritis? In nephritic MRLlpr/lpr mice, transient exposure to bacterial cell wall components such as lipopeptide or lipopolysaccharide (LPS) increased splenomegaly, the production of DNA autoantibodies, and serum interleukin (IL)-6, IL-12 and tumour necrosis factor (TNF) levels, and aggravated lupus Nephritis. Remarkably, bacterial lipopeptide induced massive albuminuria in nephritic but not in non-nephritic mice. This was associated with down-regulation of renal nephrin mRNA and redistribution from its normal localization at foot processes to the perinuclear podocyte area in nephritic MRLlpr/lpr mice. Bacterial lipopeptide activates Toll-like receptor 2 (TLR2), which we found to be expressed on cultured podocytes and glomerular endothelial cells. TNF and interferon (IFN)-γ induced TLR2 mRNA and receptor expression in both cell types. Albumin permeability was significantly increased in cultured podocytes and glomerular endothelial cells upon stimulation by bacterial lipopeptide. LPS also induced moderate albuminuria. In summary, bacterial lipopeptide and LPS can aggravate glomeruloNephritis but only lipopeptide potently induces severe albuminuria in MRLlpr/lpr mice.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.
Stephan Segerer - One of the best experts on this subject based on the ideXlab platform.
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bacterial lipopeptide triggers massive albuminuria in murine lupus Nephritis by activating toll like receptor 2 at the glomerular filtration barrier
Immunology, 2009Co-Authors: Rahul D Pawar, Liliana Castrezanalopez, Ramanjaneyulu Allam, Onkar P Kulkarni, Stephan Segerer, Ewa Radomska, Tobias N Meyer, Catherine Schwesinger, Nese Akis, Hermann Josef GroneAbstract:What are the molecular mechanisms of bacterial infections triggering or modulating lupus Nephritis? In nephritic MRLlpr/lpr mice, transient exposure to bacterial cell wall components such as lipopeptide or lipopolysaccharide (LPS) increased splenomegaly, the production of DNA autoantibodies, and serum interleukin (IL)-6, IL-12 and tumour necrosis factor (TNF) levels, and aggravated lupus Nephritis. Remarkably, bacterial lipopeptide induced massive albuminuria in nephritic but not in non-nephritic mice. This was associated with down-regulation of renal nephrin mRNA and redistribution from its normal localization at foot processes to the perinuclear podocyte area in nephritic MRLlpr/lpr mice. Bacterial lipopeptide activates Toll-like receptor 2 (TLR2), which we found to be expressed on cultured podocytes and glomerular endothelial cells. TNF and interferon (IFN)-γ induced TLR2 mRNA and receptor expression in both cell types. Albumin permeability was significantly increased in cultured podocytes and glomerular endothelial cells upon stimulation by bacterial lipopeptide. LPS also induced moderate albuminuria. In summary, bacterial lipopeptide and LPS can aggravate glomeruloNephritis but only lipopeptide potently induces severe albuminuria in MRLlpr/lpr mice.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.
Prashant S Patole - One of the best experts on this subject based on the ideXlab platform.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.
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viral double stranded rna aggravates lupus Nephritis through toll like receptor 3 on glomerular mesangial cells and antigen presenting cells
Journal of The American Society of Nephrology, 2005Co-Authors: Prashant S Patole, Matthias Kretzler, Stephan Segerer, Hermann Josef Grone, Raluca Ciubar, Emilia Belemezova, Anna Henger, Detlef Schlondorff, Hansjoachim AndersAbstract:How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL lpr/lpr mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL lpr/lpr mice, to secrete multiple proinflammatory factors. In vivo , a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-α levels. A course of 50 μg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus Nephritis in pI:C-treated MRL lpr/lpr mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL lpr/lpr mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus Nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g. , glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g. , lupus Nephritis.