Bacterial lipopeptide triggers massive albuminuria in murine lupus nephritis by activating Toll-like receptor 2 at the glomerular filtration barrier.

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.

• 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 Gröne, Hans-Joachim Anders
• Journal: Immunology (Immunology) Vol. 128 Issue 1 Suppl Pg. e206-21 (Sep 2009) ISSN: 1365-2567 [Electronic] England
• PMID: 19175801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Interleukin-6
• Lipopeptides
• Lipopolysaccharides
• Membrane Proteins
• Toll-Like Receptor 2
• Tumor Necrosis Factor-alpha
• nephrin
• Interleukin-12

Topics

• Albuminuria (immunology, metabolism, pathology)
• Animals
• Autoantibodies (blood)
• Cells, Cultured
• Endothelial Cells (drug effects, immunology, metabolism)
• Female
• Interleukin-12 (agonists, immunology, metabolism)
• Interleukin-6 (agonists, immunology, metabolism)
• Kidney (immunology, metabolism, pathology)
• Lipopeptides (immunology)
• Lipopolysaccharides (immunology)
• Lupus Nephritis (immunology, metabolism, pathology)
• Membrane Proteins (immunology, metabolism)
• Mice
• Mice, Inbred MRL lpr
• Mice, Knockout
• Podocytes (drug effects, immunology, metabolism)
• Signal Transduction (drug effects, immunology)
• Toll-Like Receptor 2 (agonists, genetics, metabolism)
• Tumor Necrosis Factor-alpha (agonists, immunology, metabolism)