Redox stress unbalances the inflammatory cytokine network: role in autoinflammatory patients and healthy subjects

[摘要] Thecellstressandredoxresponsesareincreasinglyacknowledgedasfactorscontributingtothegenerationanddevelopmentoftheinflammatoryresponse.Severalinflammation‐inducingstressorshavebeenidentified,insideandoutsideofthecell.Furthermore,manyhereditarydiseasesassociatewithinflammationandoxidativestress,suggestingaroleformutatedproteinsasstressors.Thenucleotide‐bindingoligomerizationdomain,leucine‐richrepeat‐containingfamily,pyrindomain‐containing3(NLRP3)inflammasomeisanimportantnodeatthecrossroadbetweenredoxresponseandinflammation.Remarkably,monocytesfrompatientswithmutationsintheNLRP3geneundergooxidativestressafterstimulationwithminuteamountsofTLRagonists,resultinginunbalancedproductionofIL‐1βandregulatorycytokines.SimilaralterationsincytokineproductionarefoundinhealthymonocytesuponTLRoverstimulation.Thismini‐reviewsummarizesrecentprogressinthisfield,discussesthemolecularmechanismsunderlyingthelossofcontrolofthecytokinenetworkfollowingoxidativestress,andproposesnewtherapeuticopportunities...

[学科分类] 生理学

[关键词] interleukin‐1 family;ATP secretion;TLR agonist;NLRP3 inflammasome