Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-51061

Lichtnekert, J; Kulkarni, O P; Mulay, S R; Rupanagudi, K V; Ryu, M; Allam, R; Vielhauer, V; Muruve, D; Lindenmeyer, M T; Cohen, C D; Anders, H J (2011). Anti-GBM glomerulonephritis involves IL-1 but is independent of NLRP3/ASC inflammasome-mediated activation of caspase-1. PLoS ONE, 6(10):26778.

[img]
Preview
Published Version
PDF
2MB

View at publisher

Abstract

IL-1b and IL-18 are proinflammatory cytokines that contribute to renal immune complex disease, but whether IL-1b and IL-
18 are mediators of intrinsic glomerular inflammation is unknown. In contrast to other cytokines the secretion of IL-1b and
IL-18 requires a second stimulus that activates the inflammasome-ASC-caspase-1 pathway to cleave pro-IL-1b and -IL-18
into their mature and secretable forms. As the NLRP3 inflammasome and caspase-1 were shown to contribute to
postischemic and postobstructive tubulointerstitial inflammation, we hypothesized a similar role for NLRP3, ASC, and
caspase-1 in glomerular immunopathology. This concept was supported by the finding that lack of IL-1R1 reduced
antiserum-induced focal segmental necrosis, crescent formation, and tubular atrophy when compared to wildtype mice.
Lack of IL-18 reduced tubular atrophy only. However, NLRP3-, ASC- or caspase-1-deficiency had no significant effect on renal
histopathology or proteinuria of serum nephritis. In vitro studies with mouse glomeruli or mesangial cells, glomerular
endothelial cells, and podocytes did not reveal any pro-IL-1b induction upon LPS stimulation and no caspase-1 activation
after an additional exposure to the NLRP3 agonist ATP. Only renal dendritic cells, which reside mainly in the
tubulointerstitium, expressed pro-IL-1b and were able to activate the NLRP3-caspase-1 axis and secrete mature IL-1b.
Together, the NLRP3-ASC-caspase-1 axis does not contribute to intrinsic glomerular inflammation via glomerular
parenchymal cells as these cannot produce IL-1b during sterile inflammation.

Citations

14 citations in Web of Science®
15 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

54 downloads since deposited on 17 Nov 2011
18 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:17 Nov 2011 10:11
Last Modified:29 Nov 2013 19:40
Publisher:Public Library of Science
ISSN:1932-6203
Publisher DOI:10.1371/journal.pone.0026778
PubMed ID:22046355

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page