title: 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.affiliation: Medical Policlinic, University of Munich, Munich, Germany.
authors.forename: Rahul D
authors.initials: RD
authors.lastname: Pawar
authors.forename: Liliana
authors.initials: L
authors.lastname: Castrezana-Lopez
authors.forename: Ramanjaneyulu
authors.initials: R
authors.lastname: Allam
authors.forename: Onkar P
authors.initials: OP
authors.lastname: Kulkarni
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Ewa
authors.initials: E
authors.lastname: Radomska
authors.forename: Tobias N
authors.initials: TN
authors.lastname: Meyer
authors.forename: Catherine-Meyer
authors.initials: CM
authors.lastname: Schwesinger
authors.forename: Nese
authors.initials: N
authors.lastname: Akis
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D000419:Albuminuria / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D018664:Interleukin-12 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055666:Lipopeptides / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D050199:Podocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015850:Interleukin-6; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C113267:nephrin; D018664:Interleukin-12