Skip Navigation



NDT Advance Access published online on September 5, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl336
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/11/3062    most recent
gfl336v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Patole, P. S.
Right arrow Articles by Anders, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patole, P. S.
Right arrow Articles by Anders, H.-J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 28, 2005
Accepted May 17, 2006

Original Article

Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice

Prashant S. Patole 1, Rahul D. Pawar 1, Maciej Lech 1, Daniel Zecher 1, Holger Schmidt 1, Stephan Segerer 1, Andreas Ellwart 1, Anna Henger 1, Matthias Kretzler 1, and Hans-Joachim Anders 1 *

1 Nephrological Center, Medical Policlinic, University of Munich, Munich, Germany

* To whom correspondence should be addressed.
Hans-Joachim Anders, E-mail: hjanders{at}med.uni-muenchen.de



  Abstract

Background. How microbial infections exacerbate immune complex glomerulonephritis remains speculative. Toll-like receptors (TLRs) may be involved in this phenomenon, because TLRs have potent immunostimulatory functions when exposed to selected pathogen-associated molecules.

Methods. We addressed this issue by characterizing the expression of TLR1-9 in MRLlpr/lpr mice that spontaneously develop immune complex glomerulonephritis as part of a systemic lupus-like autoimmune syndrome.

Results. Five-week-old healthy MRLlpr/lpr mice expressed TLR3 mRNA in kidneys at comparable levels as in the spleen, while all other TLRs were expressed at low levels in the kidney. In 20-week-old nephritic MRLlpr/lpr mice, renal mRNA levels had increased for TLR1-9. Renal TLR mRNA originated at least in part from glomeruli as evidenced by real-time RT-PCR from laser capture microdissected glomeruli. Immunostaining for TLR3, TLR7 and TLR9 revealed their expression by F4/80-positive infiltrating macrophages in 20-week-old nephritic MRLlpr/lpr mice. In addition, TLR3 localized to glomerular mesangial cells. Cultured mesangial cells expressed TLR1-4 and TLR6, while murine macrophages expressed TLR1-9. TNF-{alpha} and IFN-{gamma} induced TLR2, TLR3 and TLR6 mRNA in mesangial cells, while they down-regulated TLR1-9 mRNA in macrophages. Stimulation of both cell types with ligands for TLR1-4, TLR5, TLR7 and TLR9 induced IL-6 production consistent with their respective TLR expression patterns. TNF-{alpha} and IFN-{gamma} enhanced ligand-induced IL-6 production in both cell types irrespective of their modulatory effect on respective TLR mRNA levels.

Conclusion. Thus, cell-type-specific expression and regulation of TLRs may be involved in infection-associated exacerbation of immune complex glomerulonephritis of MRLlpr/lpr mice.

Keywords: autoimmune diseases; innate immunity; kidney; lupus; Toll-like receptor.

The authors wish it to be known that, in their opinion, the first two authors contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
A.-M. Fairhurst, C. Xie, Y. Fu, A. Wang, C. Boudreaux, X. J. Zhou, R. Cibotti, A. Coyle, J. E. Connolly, E. K. Wakeland, et al.
Type I Interferons Produced by Resident Renal Cells May Promote End-Organ Disease in Autoantibody-Mediated Glomerulonephritis
J. Immunol., November 15, 2009; 183(10): 6831 - 6838.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. Flur, R. Allam, D. Zecher, O. P. Kulkarni, J. Lichtnekert, M. Schwarz, B. Beutler, V. Vielhauer, and H.-J. Anders
Viral RNA Induces Type I Interferon-Dependent Cytokine Release and Cell Death in Mesangial Cells via Melanoma-Differentiation-Associated Gene-5: Implications for Viral Infection-Associated Glomerulonephritis
Am. J. Pathol., November 1, 2009; 175(5): 2014 - 2022.
[Abstract] [Full Text] [PDF]

Home page
 LupusHome page
E. Papadimitraki, M Tzardi, G Bertsias, E Sotsiou, and D. Boumpas
Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response
Lupus, August 1, 2009; 18(9): 831 - 835.
[Abstract] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Schlondorff and B. Banas
The Mesangial Cell Revisited: No Cell Is an Island
J. Am. Soc. Nephrol., June 1, 2009; 20(6): 1179 - 1187.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
K. A. Cavassani, M. Ishii, H. Wen, M. A. Schaller, P. M. Lincoln, N. W. Lukacs, C. M. Hogaboam, and S. L. Kunkel
TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events
J. Exp. Med., October 27, 2008; 205(11): 2609 - 2621.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. C. Shirali and D. R. Goldstein
Tracking the Toll of Kidney Disease
J. Am. Soc. Nephrol., August 1, 2008; 19(8): 1444 - 1450.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. C. Banas, B. Banas, K. L. Hudkins, T. A. Wietecha, M. Iyoda, E. Bock, P. Hauser, J. W. Pippin, S. J. Shankland, K. D. Smith, et al.
TLR4 Links Podocytes with the Innate Immune System to Mediate Glomerular Injury
J. Am. Soc. Nephrol., April 1, 2008; 19(4): 704 - 713.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
K. Suzuki, T. Imaizumi, K. Tsugawa, E. Ito, and H. Tanaka
Expression of retinoic acid-inducible gene-I in lupus nephritis
Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2407 - 2409.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
R. D. Pawar, A. Ramanjaneyulu, O. P. Kulkarni, M. Lech, S. Segerer, and H.-J. Anders
Inhibition of Toll-Like Receptor-7 (TLR-7) or TLR-7 plus TLR-9 Attenuates Glomerulonephritis and Lung Injury in Experimental Lupus
J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1721 - 1731.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.