Banas, Miriam C. and Banas, Bernhard and Hudkins, Kelly L. and Wietecha, Tomasz A. and Iyoda, Masayuki and Bock, Elisabeth and Hauser, Peter and Pippin, Jeffrey W. and Shankland, Stuart J. and Smith, Kelly D. and Stoelcker, Benjamin and Liu, Gang and Groene, Hermann-Josef and Kraemer, Bernhard K. and Alpers, Charles E. (2008) TLR4 links podocytes with the innate immune system to mediate glomerular injury. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 19 (4). pp. 704-713. ISSN 1046-6673,
Full text not available from this repository. (Request a copy)Abstract
Toll-like receptors (TLR) classically recognize pathogen-associated danger signals but are also activated via endogenous ligands. For evaluation of their role in inflammatory kidney disease, the function of TLR was analyzed in two mouse models of cryoglobulinemic membranoproliferative glomerulonephritis (MPGN; mice transgenic for thymic stromal lymphopoietin [TSLP] with or without deletion of the Fc gamma receptor IIb). Expression of TLR1 through 9 and TLR1 1 mRNA was detectable in whole kidneys and in isolated glomeruli of wild-type mice, with TLR3 and TLR4 having the highest absolute levels of expression. TLR1, 2, and 4 were increased in TSLP transgenic mice and even higher in TSLP transgenic Fc gamma RIIb-deficient mice. TLR5 through 9 and 11 were upregulated to similar degrees in TSLP transgenic and TSLP transgenic Fc gamma RIIb-deficient mice. Immunohistochemical studies of nephritic glomeruli localized TLR4 protein to podocytes. Cultured podocytes also expressed TLR4, and stimulation with TLR4-specific ligands resulted in a marked induction of chemokines; this was reduced by specific knockdown of TLR4 with siRNA. Fibrinogen, a potential endogenous TLR4 ligand, was shown to induce a similar profile of chemokines. In conclusion, it was demonstrated that TLR4 is constitutively expressed by podocytes and is upregulated in MPGN, where it may mediate glomerular injury by modulating expression of chemokines; therefore, TLR4 may link podocytes with the innate immune system to mediate MPGN triggered by the deposition of immune complexes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TOLL-LIKE RECEPTORS; THYMIC STROMAL LYMPHOPOIETIN; MATURE HUMAN KIDNEY; COMPLEX GLOMERULONEPHRITIS; EPITHELIAL-CELLS; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; MRL-FAS(LPR) MICE; KINASE-INHIBITOR; TRANSGENIC MICE; IN-VITRO; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Nov 2020 07:38 |
| Last Modified: | 05 Nov 2020 07:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31126 |
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