HMGB1的受体HMGB1IL-1BRNAand DNACXCL12LPSNucleosomes000CThrombo.spondinTLR4MD-2NTLR2TREM-1CD2400002IL-1R+MD2IL-1RACPRAGEGPCRTLR9TLR7DNAEndosomeRNASimsGP,etal.2olo.Annu.Rev.Immunol.28:367-88HMGB1-associatedmoleculesanddifferentialinteractionwithcell-surfacemolecules
HMGB1-associated molecules and differential interaction with cell-surface molecules HMGB1的受体
OHMGB1*胞外HMGB1的受体C1糖基化终产物受体（advancedC2glycation end product, RAGE)HMGB1与RAGE结合→激活NF- BPKCRap1→诱生趋化因子和细胞因子ERK12Dapanous.Pleckstrin参与免疫细胞成熟、迁移Regulationofcytoskeleton和表面受体表达andcellNADPHCDC42migrationRacActivationOfSP1RasHMGB1与TLR2/4结合p30UNKERK112活化IKKa和IKKβActivationofActivation ofNF-KBCREBRegulationoftranscription
* 胞外HMGB1的受体 糖基化终产物受体（advanced glycation end product，RAGE） HMGB1与RAGE结合 →激活NF-κB →诱生趋化因子和细胞因子 参与免疫细胞成熟、迁移 和表面受体表达 HMGB1与TLR2/4结合 →活化IKKａ和IKKβ
Enhanceproinflammatorycytokinessecretion,maturation,cytokinesecretion,andco-stimulatorycapabilityTNF-aIFN-YLPS21TLR4CPGODNAImmatureMdTLR4IFN-O.TLR9AMyloidDCNFKBHNLPS1Plasmacytoid个DCRAGE.RAGERAGE个ActivesecretionoCIFN-Y4HMGBICO.8CD4+NKTcellsBcl-XLPreventautoreactiveimmunecelleliminationFunctionofExtracellularHMGB1
Bcl-X L LPS RAGE TNF-α IFN-γ TLR4 LPS N K CD4+ T cells RAGE IFN-α IFN-γ Prevent autoreactive immune cell elimination Enhance proinflammatory cytokines secretion, maturation, cytokine secretion, and co-stimulatory capability Immature Myloid DC RAGE TLR9 CpG ODN Plasmacytoid D C NF κ B Active secretion TLR4 HMGB1 MΦ NF κ B Function of Extracellular HMGB1
HMGB1表达/分泌的调控机制“HMGB1-MΦ-TNF-α-MΦ-HMGB1”正反馈机制*HMGB1→显著上调巨噬细胞表达TNF-α* TNF-α →MΦ胞核内HMGB1磷酸化→进入胞浆→分泌LPS等（PAMP）→HMGB1乙酰化→分泌HSP72过表达→与核内HMGB1相互作用→抑制LPS、TNFα和氧化应激促MΦ分泌HMGB1的效应（inflammasomeNALP3炎症小体→炎症依赖性HMGB1释放IDO、HO-1→HMGB1释放减少
HMGB1表达/分泌的调控机制 “HMGB1-Mφ-TNF-α-Mφ-HMGB1”正反馈机制 * HMGB1→显著上调巨噬细胞表达TNF-α * TNF-α→Mφ胞核内HMGB1磷酸化→进入胞浆→分泌 LPS等（PAMP） →HMGB1乙酰化→分泌 HSP72过表达 →与核内HMGB1相互作用 →抑制LPS、TNFα和氧化应激促Mφ分泌HMGB1的效应 NALP3炎症小体（inflammasome） →炎症依赖性HMGB1释放 IDO、HO-1 →HMGB1释放减少
LPS.Pam3CSK4R848,CpGTLRATPPlasmamembraneYCytosolP2X7receptorInflamasome-DependentK.AeromonashydrophilaGoutcrystalsRelease of HGBiBacterialRNAListeriamonocytogenesStaphylococcusaureus.ToxinsNALP3inflammasomeInactiveNALP3LRROligomerizationActivecaspase-lNACHTdomainPYDProteolyticcleavageASCCARDPro-caspase-1IL-IBMacrophagecell deathand IL-18NatureReviewsllmmunologyActivationoftheNALP3inflammasomebybacterialandhost-derivedcomponents
Activation of the NALP3 inflammasome by bacterial and host-derived components