Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-9-9
pubmed:abstractText
Myeloperoxidase (MPO)-anti-neutrophil cytoplasmic autoantibody (ANCA)-associated necrotizing crescentic glomerulonephritis (NCGN) is characterized by abundant leucocyte infiltration. Chemokines are chemotactic cytokines involved in receptor-mediated recruitment of leucocytes. Our objective was to analyse spatiotemporal gene expression of chemokines and chemokine receptors in anti-MPO-mediated NCGN, to find potential targets for intervening with leucocyte influx. NCGN was induced in mice by co-administration of anti-MPO immunoglobulin (Ig)G and lipopolysaccharide. mRNA expression levels of chemokines and chemokine receptors were analysed in whole kidney lysates as well as in laser microdissected glomeruli and tubulo-interstitial tissue 1 and 7 day(s) after NCGN induction. Several chemokines and chemokine receptors were induced or up-regulated in anti-MPO-mediated NCGN, both on day 1 (chemokines CCL3, 5; CXCL2, 5, 13; receptor CXCR2) and on day 7 (chemokines CCL2, 5, 7, 8, 17, 20; CXCL1, 2, 5, 10; CX(3)CL1; receptors CCR2, 8; CX(3)CR1). The expression levels of most chemokines and receptors were higher in glomeruli than in the tubulo-interstitium. Because of the temporal induction of CXCR2 on day 1, we hypothesized CXCR2 as a potential target for treatment in anti-MPO-induced NCGN. Inhibition of CXCR2 using a goat-anti-CXCR2 serum prior to NCGN induction increased glomerular neutrophil influx but did not affect crescent formation and albuminuria. In conclusion, expression levels of various chemokines and chemokine receptors were increased in anti-MPO NCGN, and expressed particularly in glomeruli. These chemokines and receptors may serve as potential targets for treatment. Inhibition of a single target, CXCR2, did not attenuate anti-MPO NCGN. Combinatorial interventions may be necessary to avoid redundancy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1365-2249
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
158
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-53
pubmed:dateRevised
2010-10-4
pubmed:meshHeading
pubmed-meshheading:19737241-Animals, pubmed-meshheading:19737241-Antibodies, Antineutrophil Cytoplasmic, pubmed-meshheading:19737241-Chemokine CXCL1, pubmed-meshheading:19737241-Chemokine CXCL2, pubmed-meshheading:19737241-Chemokine CXCL5, pubmed-meshheading:19737241-Chemokines, pubmed-meshheading:19737241-Endothelial Cells, pubmed-meshheading:19737241-Female, pubmed-meshheading:19737241-Gene Expression, pubmed-meshheading:19737241-Gene Expression Regulation, pubmed-meshheading:19737241-Glomerulonephritis, pubmed-meshheading:19737241-Immune Sera, pubmed-meshheading:19737241-Immunoglobulin G, pubmed-meshheading:19737241-Kidney Glomerulus, pubmed-meshheading:19737241-Kidney Tubules, pubmed-meshheading:19737241-Lipopolysaccharides, pubmed-meshheading:19737241-Mice, pubmed-meshheading:19737241-Mice, Inbred C57BL, pubmed-meshheading:19737241-Mice, Knockout, pubmed-meshheading:19737241-Models, Animal, pubmed-meshheading:19737241-Neutrophils, pubmed-meshheading:19737241-Peroxidase, pubmed-meshheading:19737241-Receptors, Chemokine, pubmed-meshheading:19737241-Receptors, Interleukin-8B, pubmed-meshheading:19737241-Time Factors
pubmed:year
2009
pubmed:articleTitle
Spatiotemporal expression of chemokines and chemokine receptors in experimental anti-myeloperoxidase antibody-mediated glomerulonephritis.
pubmed:affiliation
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't