P2X7 receptor‐mediated Nlrp3‐inflammasome activation is a genetic determinant of macrophage‐dependent crescentic glomerulonephritis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: WKY rat;    IL‐;    1β;    caspase‐;    1;    IL‐;    18;    glomeruli;   

DOI  :  10.1189/jlb.0612284

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

P2RX7,amediatorofIL‐1βandIL‐18processingandrelease,isaligand‐gatedcationchannelthatisexpressedbymacrophages.InexperimentalCrgn,P2RX7deficiencyattenuatesrenalinjury,buttheunderlyingmechanismisunknown.Here,weshowthatP2RX7levelsandtheexpressionofseveralgenesbelongingtotheNlrp3‐inflammasomepathwayareup‐regulatedinthemacrophagesoftheWKYrat,astrainuniquelysusceptibletomacrophage‐dependentNTN.Importantly,followingP2RX7activation,WKYBMDMsproducemarkedlyincreasedlevelsofactivecaspase‐1,IL‐1β,andIL‐18whencomparedwiththeNTN‐resistantLEWratBMDMs.P2RX7andactiveIL‐1β,IL‐18,andcaspase‐1proteinlevelsweremarkedlyincreasedintheWKYnephriticglomeruli4daysfollowinginductionofNTN,andtheuseofaP2RX7antagonistreducedthelevelsofsecretedactiveIL‐1β.Interestingly,thepost‐translationalcontrolofP2RX7‐mediatedinflammasomeactivationisunderthegeneticregulationoftwopreviouslyidentifiedCrgnquantitativetraitlociintheBMDMsandnephriticglomerulioftheWKYrat.Inconclusion,weproposeanovelmechanism,wherebygeneticallydeterminedP2RX7levelsinmacrophagesregulateNlrp3‐inflammasomeactivationandsusceptibilitytoCrgn...

【 授权许可】

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