Imperial College London
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ProfessorFrederickTam

Faculty of Medicine, Department of Immunology and Inflammation

Ken and Mary Minton Chair of Renal Medicine
 
 
 
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Contact

 

+44 (0)20 3313 2354f.tam

 
 
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Location

 

9N, 15C, Commonwealth BuildingHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Luz:2019:10.1038/s41598-019-56560-2,
author = {Luz, HL and Reichel, M and Unwin, RJ and Mutig, K and Najenson, AC and Tonner, LM and Eckardt, K-U and Tam, FWK and Knauf, F},
doi = {10.1038/s41598-019-56560-2},
journal = {Scientific Reports},
title = {P2X7 receptor stimulation is not required for oxalate crystal-induced kidney injury},
url = {http://dx.doi.org/10.1038/s41598-019-56560-2},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Oxalate crystal-induced renal inflammation is associated with progressive kidney failure due to activation of the NLRP3/CASP-1 inflammasome. It has been suggested previously that purinergic P2X7 receptor signaling is critical for crystal-induced inflammasome activation and renal injury. Therefore, we investigated the role of the P2X7 receptor in response to crystal-induced cytokine release, inflammation, and kidney failure using in vitro and in vivo models. Dendritic cells and macrophages derived from murine bone marrow and human peripheral blood mononucleated cells stimulated with calcium-oxalate crystals, monosodium urate crystals, or ATP lead to the robust release of interleukin-1beta (IL-1ß). Treatment with the P2X7 inhibitor A740003 or the depletion of ATP by apyrase selectively abrogated ATP-induced, but not oxalate and urate crystal-induced IL-1ß release. In line with this finding, dendritic cells derived from bone marrow (BMDCs) from P2X7-/- mice released reduced amounts of IL-1ß following stimulation with ATP, while oxalate and urate crystal-induced IL-1ß release was unaffected. In sharp contrast, BMDCs from Casp1-/- mice exhibited reduced IL-1ß release following either of the three stimulants. In addition, P2X7-/- mice demonstrated similar degrees of crystal deposition, tubular damage and inflammation when compared with WT mice. In line with these findings, increases in plasma creatinine were no different between WT and P2X7-/- mice. In contrast to previous reports, our results indicate that P2X7 receptor is not required for crystal-induced CKD and it is unlikely to be a suitable therapeutic target for crystal-induced progressive kidney disease.
AU  - Luz,HL
AU  - Reichel,M
AU  - Unwin,RJ
AU  - Mutig,K
AU  - Najenson,AC
AU  - Tonner,LM
AU  - Eckardt,K-U
AU  - Tam,FWK
AU  - Knauf,F
DO  - 10.1038/s41598-019-56560-2
PY  - 2019///
SN  - 2045-2322
TI  - P2X7 receptor stimulation is not required for oxalate crystal-induced kidney injury
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-56560-2
UR  - http://hdl.handle.net/10044/1/75488
VL  - 9
ER  -
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