P2X7 Receptor Stimulation Is Not Required for Oxalate Crystal-Induced Kidney Injury.

摘要: 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 critical for inflammasome and injury. Therefore, we investigated role in response cytokine release, inflammation, using vitro vivo models. Dendritic cells macrophages derived from murine bone marrow human peripheral blood mononucleated stimulated calcium-oxalate crystals, monosodium urate or ATP lead robust release interleukin-1beta (IL-1s). Treatment inhibitor A740003 depletion by apyrase selectively abrogated ATP-induced, but not oxalate IL-1s release. In line this finding, dendritic (BMDCs) P2X7-/- mice released reduced amounts following stimulation ATP, while was unaffected. sharp contrast, BMDCs Casp1-/- exhibited either three stimulants. addition, demonstrated similar degrees crystal deposition, tubular damage when compared WT mice. these findings, increases plasma creatinine were no different between contrast previous reports, our results indicate required CKD it unlikely be a suitable therapeutic target disease.