scholarly journals Double-Stranded DNA Activates Glomerular Endothelial Cells and Enhances Albumin Permeability via a Toll-Like Receptor-Independent Cytosolic DNA Recognition Pathway

2009 ◽  
Vol 175 (5) ◽  
pp. 1896-1904 ◽  
Author(s):  
Holger Hägele ◽  
Ramanjaneyulu Allam ◽  
Rahul D. Pawar ◽  
Christoph A. Reichel ◽  
Fritz Krombach ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Dna Recognition ◽  
Toll Like Receptor ◽  
Double Stranded Dna ◽  
Glomerular Endothelial Cells

scholarly journals Cytosolic Sensors of Viral RNA Are Involved in the Production of Interleukin-6 via Toll-Like Receptor 3 Signaling in Human Glomerular Endothelial Cells

2019 ◽  
Vol 44 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Qiang Liu ◽  
Tadaatsu Imaizumi ◽  
Tomomi Aizawa ◽  
Koji Hirono ◽  
Shogo Kawaguchi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Interleukin 6 ◽  
Viral Rna ◽  
Pivotal Role ◽  
Toll Like Receptor ◽  
Polycytidylic Acid ◽  
Glomerular Endothelial Cells ◽  
Human Glomerular Endothelial Cells ◽  
Tlr3 Signaling

Background/Aims: Dysregulation of interleukin-6 (IL-6) production in residual renal cells may play a pivotal role in the development of glomerulonephritis (GN). Given that Toll-like receptor 3 (TLR3) signaling has been implicated in the pathogenesis of some forms of GN, we examined activated TLR3-mediated IL-6 signaling in cultured normal human glomerular endothelial cells (GECs). Methods: We treated GECs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expression of IL-6 and the cytosolic viral RNA sensors retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) using reverse transcription quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays. To further elucidate the effects of poly IC on this signaling pathway, we subjected the cells to small interfering RNA (siRNA) against TLR3, interferon (IFN)-β, RIG-I, and MDA5. Results: We found that poly IC induced the expression of RIG-I, MDA5 and IL-6 via TLR3/IFN-β signaling in GECs. siRNA experiments revealed that both MDA5 and RIG-I were involved in the poly IC-induced expression of IL-6, with MDA5 being upstream of RIG-I. Conclusion: Interestingly, cytosolic sensors of viral RNA were found to be involved in IL-6 production via TLR3 signaling in GECs. Regional activation of TLR3/IFN-β/ MDA5/RIG-I/IL-6 axis due to viral and “pseudoviral” infections is involved in innate immunity and inflammatory reactions in GECs. We believe this signaling pathway also plays a pivotal role in the development of some forms of GN.

scholarly journals Expression of Toll-Like Receptor 4 in Glomerular Endothelial Cells under Diabetic Conditions

2013 ◽  
Vol 46 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Shunsuke Takata ◽  
Yoshihiko Sawa ◽  
Takanobu Uchiyama ◽  
Hiroyuki Ishikawa
Keyword(s):  
Endothelial Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Glomerular Endothelial Cells

scholarly journals IFIT Proteins Are Involved in CXCL10 Expression in Human Glomerular Endothelial Cells Treated with a Toll-Like Receptor 3 Agonist

2020 ◽  
pp. 1-12
Author(s):  
Tadaatsu Imaizumi ◽  
Shun Hashimoto ◽  
Riko Sato ◽  
Hidenori Umetsu ◽  
Tomomi Aizawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Tetratricopeptide Repeats ◽  
Immune Reactions ◽  
Polycytidylic Acid ◽  
Glomerular Endothelial Cells ◽  
Chemokine Ligand ◽  
Human Glomerular Endothelial Cells ◽  
Novel Coronavirus

Introduction: Various viruses including a novel coronavirus (SARS-CoV-2) can infect the kidney. When viruses invade the glomeruli from the bloodstream, glomerular endothelial cells (GECs) initiate the innate immune reactions. We investigated the expression of interferon (IFN)-induced protein with tetratricopeptide repeats (IFIT) 1/2/3, antiviral molecules, in human GECs treated with a toll-like receptor (TLR) 3 agonist. Role of IFIT1/2/3 in the expression of C-X-C motif chemokine ligand 10 (CXCL10) was also examined. Methods: Human GECs were cultured and stimulated with polyinosinic-polycytidylic acid (poly IC), a synthetic TLR3 agonist. Real-time qPCR, Western blotting, and ELISA were used to examine the expression of IFIT1/2/3, IFN-β, and CXCL10. RNA interference against IFN-β or IFIT1/2/3 was also performed. Results: Expression of IFIT1/2/3 and CXCL10 was induced by poly IC in GECs. The inductions were inhibited by RNA interfering of IFN-β. Knockdown of IFIT1/2/3 decreased the CXCL10 expression. Knockdown of IFIT3 decreased the expression of IFIT1 and IFIT2 proteins. Conclusion: IFIT1/2/3 and CXCL10 were induced by poly IC via IFN-β in GECs. IFIT1/2/3 may increase the expression of CXCL10 which induces lymphocyte chemotaxis and may inhibit the replication of infected viruses. These molecules may play a role in GEC innate immune reactions in response to viruses.

Endothelial expression of fractalkine (CX3CL1) is induced by Toll-like receptor 3 signaling in cultured human glomerular endothelial cells

2019 ◽  
Vol 30 (6) ◽  
pp. 1074-1081
Author(s):  
Koji Hirono ◽  
Tadaatsu Imaizumi ◽  
Tomomi Aizawa ◽  
Shojiro Watanabe ◽  
Koji Tsugawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Toll Like Receptor ◽  
Glomerular Endothelial Cells ◽  
Human Glomerular Endothelial Cells

Autoantibodies Against Human Renal Glomerular Endothelial Cells in Lupus Nephritis That Induce Endothelial Interferon-Alpha Production

2020 ◽  
Author(s):  
Ya-Chiao Hu ◽  
I-Jung Tsai ◽  
Hui-Yao Hsu ◽  
Bor-Luen Chiang ◽  
Yao-Hsu Yang
Keyword(s):  
Endothelial Cells ◽  
Monoclonal Antibodies ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Double Stranded Dna ◽  
Glomerular Endothelial Cells ◽  
Dnase 1

Abstract Background: The pathogenesis of lupus nephritis (LN) remains not fully understood. In this study, we aimed to explore the pathogenic roles of autoantibodies against human renal glomerular endothelial cells (HRGEC) in LN patients.Methods: The serum levels of anti-HRGEC antibodies in systemic lupus erythematosus (SLE) patients without LN and LN patients were determined by cell-based enzyme-linked immunosorbent assay (ELISA). Monoclonal IgG anti-HRGEC antibodies were subsequently generated from LN patients. The binding activities of these monoclonal antibodies to HRGEC, their cross-reactivity with double-stranded DNA (dsDNA), and the ability to activate HRGEC were further evaluated. Results: LN patients had higher serum levels of IgG anti-HRGEC antibodies than SLE patients without LN and healthy controls. Four monoclonal IgG anti-HRGEC antibodies (LN1-4) were obtained; LN1 and LN2 were IgG3 while LN3 and LN4 were IgG1. Among these monoclonal antibodies, LN1-3 were cross-reactive with dsDNA. The functional assays showed that compared with IgG1/IgG3 isotype controls, LN3 had the effect on HRGEC to enhance interleukin (IL)-6 production, LN4 could enhance IL-8 and monocyte chemoattractant protein (MCP)-1 production, and LN1-3 possessed the ability to induce interferon (IFN)-α production by HRGEC. Moreover, the removal of DNA on HRGEC surface by DNAse 1 did not interpose the binding of LN1-3 to HRGEC and the effects of LN1-3 on IFN-α induction by HRGEC.Conclusions: Some IgG anti-HRGEC antibodies in LN patients had the ability to enhance endothelial proinflammatory cytokines (IL-6, IL-8, and MCP-1) production and some could induce the DNA-independent production of IFN-α by HRGEC.

Toll-Like Receptor 3 Signaling Contributes to Regional Neutrophil Recruitment in Cultured Human Glomerular Endothelial Cells

Nephron ◽  
2018 ◽  
Vol 139 (4) ◽  
pp. 349-358 ◽  
Author(s):  
Qiang Liu ◽  
Tadaatsu Imaizumi ◽  
Shogo Kawaguchi ◽  
Tomomi Aizawa ◽  
Tomoh Matsumiya ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neutrophil Recruitment ◽  
Toll Like Receptor ◽  
Glomerular Endothelial Cells ◽  
Human Glomerular Endothelial Cells

scholarly journals Identification of monoclonal antibodies against human renal glomerular endothelial cells in lupus nephritis that induce endothelial interferon-alpha production

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Ya-Chiao Hu ◽  
I-Jung Tsai ◽  
Hui-Yao Hsu ◽  
Bor-Luen Chiang ◽  
Yao-Hsu Yang
Keyword(s):  
Endothelial Cells ◽  
Monoclonal Antibodies ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Double Stranded Dna ◽  
Glomerular Endothelial Cells ◽  
Dnase 1

Abstract Background The pathogenesis of lupus nephritis (LN) remains not fully understood. In this study, we aimed to explore the pathogenic roles of autoantibodies against human renal glomerular endothelial cells (HRGEC) in LN patients. Methods The serum levels of anti-HRGEC antibodies in systemic lupus erythematosus (SLE) patients without LN and LN patients were determined by cell-based enzyme-linked immunosorbent assay (ELISA). Monoclonal IgG anti-HRGEC antibodies were subsequently generated from LN patients. The binding activities of these monoclonal antibodies to HRGEC, their cross-reactivity with double-stranded DNA (dsDNA), and the ability to activate HRGEC were further evaluated. Results LN patients had higher serum levels of IgG anti-HRGEC antibodies than SLE patients without LN and healthy controls. Four monoclonal IgG anti-HRGEC antibodies (LN1–4) were obtained; LN1 and LN2 were IgG3 while LN3 and LN4 were IgG1. Among these monoclonal antibodies, LN1–3 were cross-reactive with dsDNA. The functional assays showed that compared with IgG1/IgG3 isotype controls, LN3 had an effect on HRGEC to enhance interleukin (IL)-6 production, LN4 could enhance IL-8 and monocyte chemoattractant protein (MCP)-1 production, and LN1–3 possessed the ability to induce interferon (IFN)-α production by HRGEC. Moreover, the removal of DNA on the HRGEC surface by DNAse 1 did not interpose the binding of LN1–3 to HRGEC and the effects of LN1–3 on IFN-α induction by HRGEC. Conclusions Some IgG anti-HRGEC antibodies in LN patients had the ability to enhance endothelial proinflammatory cytokine (IL-6, IL-8, and MCP-1) production, and some could induce the DNA-independent production of IFN-α by HRGEC.

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