RGD Reference Report - Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis. - Rat Genome Database

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Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis.

Authors: Summers, SA  Van der Veen, BS  O'Sullivan, KM  Gan, PY  Ooi, JD  Heeringa, P  Satchell, SC  Mathieson, PW  Saleem, MA  Visvanathan, K  Holdsworth, SR  Kitching, AR 
Citation: Summers SA, etal., Kidney Int. 2010 Sep 15.
RGD ID: 4144104
Pubmed: PMID:20844472   (View Abstract at PubMed)
DOI: DOI:10.1038/ki.2010.327   (Journal Full-text)

Antimyeloperoxidase antibodies can cause crescentic glomerulonephritis and pulmonary hemorrhage. Toll-like receptors (TLRs) respond to infectious agents activating host defenses, whereas infections potentially initiate disease and provoke relapses. Neutrophils were found to be key effector cells of injury in experimental models, as disease does not occur in their absence and injury is enhanced by lipopolysaccharide (LPS). In this study, highly purified LPS (a pure TLR4 ligand) acted with antimyeloperoxidase antibodies to synergistically increase kidney and lung neutrophil recruitment and functional injury; effects abrogated in TLR4-deficient mice. Increased kidney TLR4 expression after stimulation predominantly occurred in glomerular endothelial cells. Enhanced glomerular neutrophil recruitment correlated with increased kidney mRNA expression of CXCL1 and CXCL2 (homologs of human CXCL8), whereas their preemptive neutralization decreased neutrophil recruitment. Disease induction in bone marrow chimeric mice showed that TLR4 in both bone marrow and renal parenchymal cells is required for maximal neutrophil recruitment and glomerular injury. Further studies in human glomerular cell lines stimulated with LPS found that glomerular endothelial cells were the prominent sources of CXCL8. Thus, our results define a role for TLR4 expression in bone marrow-derived and glomerular endothelial cells in neutrophil recruitment and subsequent functional and histological renal injury in experimental antimyeloperoxidase glomerulonephritis.Kidney International advance online publication, 15 September 2010; doi:10.1038/ki.2010.327.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glomerulonephritis  ISOTlr4 (Mus musculus)4144104; 4144104 RGD 
glomerulonephritis  IMP 4144104 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
TLR4  (toll like receptor 4)


Additional Information