Bacterial Lipopeptide Triggers Massive Albuminuria in Murine Lupus Nephritis by Activating Toll-like Receptor 2 at the Glomerular Filtration Barrier

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2009 Jan 30

PMID 19175801

Citations 42

Authors

Rahul D Pawar

Liliana Castrezana-Lopez

Ramanjaneyulu Allam

Onkar P Kulkarni

Stephan Segerer

Ewa Radomska

Tobias N Meyer

Catherine-Meyer Schwesinger

Nese Akis

Hermann-Josef Grone

Hans-Joachim Anders

Affiliations

Soon will be listed here.

Abstract

What are the molecular mechanisms of bacterial infections triggering or modulating lupus nephritis? In nephritic MRL(lpr/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 MRL(lpr/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)-gamma 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 MRL(lpr/lpr) mice.

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References

Pawar R, Patole P, Zecher D, Segerer S, Kretzler M, Schlondorff D . Toll-like receptor-7 modulates immune complex glomerulonephritis. J Am Soc Nephrol. 2005; 17(1):141-9. DOI: 10.1681/ASN.2005070714. View

Wornle M, Schmid H, Banas B, Merkle M, Henger A, Roeder M . Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis. Am J Pathol. 2006; 168(2):370-85. PMC: 1606499. DOI: 10.2353/ajpath.2006.050491. View

Brooks T, Hawkins B, Huber J, Egleton R, Davis T . Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations. Am J Physiol Heart Circ Physiol. 2005; 289(2):H738-43. PMC: 4638185. DOI: 10.1152/ajpheart.01288.2004. View

Hawkins B, Abbruscato T, Egleton R, Brown R, Huber J, Campos C . Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution. Brain Res. 2004; 1027(1-2):48-58. DOI: 10.1016/j.brainres.2004.08.043. View

Janeway Jr C, Medzhitov R . Innate immune recognition. Annu Rev Immunol. 2002; 20:197-216. DOI: 10.1146/annurev.immunol.20.083001.084359. View

Brown H, Lock H, Sacks S, Robson M . TLR2 stimulation of intrinsic renal cells in the induction of immune-mediated glomerulonephritis. J Immunol. 2006; 177(3):1925-31. DOI: 10.4049/jimmunol.177.3.1925. View

Camici M . Renal glomerular permselectivity and vascular endothelium. Biomed Pharmacother. 2005; 59(1-2):30-7. DOI: 10.1016/j.biopha.2004.06.003. View

Weening J, DAgati V, Schwartz M, Seshan S, Alpers C, Appel G . The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004; 65(2):521-30. DOI: 10.1111/j.1523-1755.2004.00443.x. View

Akira S, Uematsu S, Takeuchi O . Pathogen recognition and innate immunity. Cell. 2006; 124(4):783-801. DOI: 10.1016/j.cell.2006.02.015. View

10.

Tryggvason K, Patrakka J, Wartiovaara J . Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006; 354(13):1387-401. DOI: 10.1056/NEJMra052131. View

11.

Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K . Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002; 3(2):196-200. DOI: 10.1038/ni758. View

12.

Aliprantis A, Yang R, Mark M, Suggett S, Devaux B, Radolf J . Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science. 1999; 285(5428):736-9. DOI: 10.1126/science.285.5428.736. View

13.

Akis N, Madaio M . Isolation, culture, and characterization of endothelial cells from mouse glomeruli. Kidney Int. 2004; 65(6):2223-7. DOI: 10.1111/j.1523-1755.2004.00634.x. View

14.

Shankland S, Pippin J, Reiser J, Mundel P . Podocytes in culture: past, present, and future. Kidney Int. 2007; 72(1):26-36. DOI: 10.1038/sj.ki.5002291. View

15.

Pawar R, Patole P, Ellwart A, Lech M, Segerer S, Schlondorff D . Ligands to nucleic acid-specific toll-like receptors and the onset of lupus nephritis. J Am Soc Nephrol. 2006; 17(12):3365-73. DOI: 10.1681/ASN.2006030263. View

16.

Angelini D, Hyun S, Grigoryev D, Garg P, Gong P, Singh I . TNF-alpha increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia. Am J Physiol Lung Cell Mol Physiol. 2006; 291(6):L1232-45. DOI: 10.1152/ajplung.00109.2006. View

17.

Anders H, Banas B, Linde Y, Weller L, Cohen C, Kretzler M . Bacterial CpG-DNA aggravates immune complex glomerulonephritis: role of TLR9-mediated expression of chemokines and chemokine receptors. J Am Soc Nephrol. 2003; 14(2):317-26. DOI: 10.1097/01.asn.0000042169.23931.73. View

18.

Mundel P, Reiser J, Zuniga Mejia Borja A, Pavenstadt H, Davidson G, Kriz W . Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalized mouse podocyte cell lines. Exp Cell Res. 1997; 236(1):248-58. DOI: 10.1006/excr.1997.3739. View

19.

Anders H, Vielhauer V, Eis V, Linde Y, Kretzler M, Perez De Lema G . Activation of toll-like receptor-9 induces progression of renal disease in MRL-Fas(lpr) mice. FASEB J. 2004; 18(3):534-6. DOI: 10.1096/fj.03-0646fje. View

20.

Wang W, DENTLER W, Borchardt R . VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly. Am J Physiol Heart Circ Physiol. 2000; 280(1):H434-40. DOI: 10.1152/ajpheart.2001.280.1.H434. View