Polyhydroxylated Metallofullerenols Stimulate IL-1 beta Secretion of Macrophage through TLRs/MyD88/NF-kappa B Pathway and NLRP3 Inflammasome Activation
Chen ZY(谌志筠); Liu Y(刘颖); 孙宝云;Chen, ZY; Liu, Y; Sun, BY; Li, H; Dong, JQ; Zhang, LJ; Wang, LM; Wang, P; Zhao, YL; Chen, CY; Li H(李菡); Dong JQ(董金泉); Wang LM(王黎明); Wang P(王鹏); Zhao YL(赵宇亮); Chen CY(陈春英)
刊名SMALL
2014
卷号10期号:12页码:2362-2372
学科分类Chemistry; Science & Technology - Other Topics; Materials Science; Physics
DOI10.1002/smll.201302825
英文摘要Polyhydroxylated fullerenols especially gadolinium endohedral metallofullerenols (Gd@C-82(OH)(22)) are shown as a promising agent for antitumor chemotherapeutics and good immunoregulatory effects with low toxicity. However, their underlying mechanism remains largely unclear. We found for the first time the persistent uptake and subcellular distribution of metallofullerenols in macrophages by taking advantages of synchrotron-based scanning transmission X-ray microscopy (STXM) with high spatial resolution of 30 nm. Gd@C-82(OH)(22) can significantly activate primary mouse macrophages to produce pro-inflammatory cytokines like IL-1 beta. Small interfering RNA (siRNA) knockdown shows that NLRP3 inflammasomes, but not NLRC4, participate in fullerenol-induced IL-1 beta production. Potassium efflux, activation of P2X(7) receptor and intracellular reactive oxygen speciesare also important factors required for fullerenols-induced IL-1 beta release. Stronger NF-kappa B signal triggered by Gd@C-82(OH)(22) is in agreement with higher pro-IL-1 beta expression than C-60(OH)(22). Interestingly, TLR4/MyD88 pathway but not TLR2 mediates IL-1 beta secretion in Gd@C-82(OH)(22) exposure confirmed by macrophages from MyD88(-/-)/TLR4(-/-)/TLR2(-/-) knockout mice, which is different from C-60(OH)(22). Our work demonstrated that fullerenols can greatly activate macrophage and promote IL-1 beta production via both TLRs/MyD88/NF-kappa B pathway and NLRP3 inflammasome activation, while Gd@C-82(OH)(22) had stronger ability C-60(OH)(22) due to the different electron affinity on the surface of carbon cage induced by the encaged gadolinium ion.
收录类别SCI
WOS记录号WOS:000337801200009
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被引频次:23[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/225372
专题中国科学院高能物理研究所_多学科研究中心_期刊论文
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GB/T 7714
Chen ZY,Liu Y,孙宝云;Chen, ZY,et al. Polyhydroxylated Metallofullerenols Stimulate IL-1 beta Secretion of Macrophage through TLRs/MyD88/NF-kappa B Pathway and NLRP3 Inflammasome Activation[J]. SMALL,2014,10(12):2362-2372.
APA 谌志筠.,刘颖.,孙宝云;Chen, ZY.,Liu, Y.,Sun, BY.,...&陈春英.(2014).Polyhydroxylated Metallofullerenols Stimulate IL-1 beta Secretion of Macrophage through TLRs/MyD88/NF-kappa B Pathway and NLRP3 Inflammasome Activation.SMALL,10(12),2362-2372.
MLA 谌志筠,et al."Polyhydroxylated Metallofullerenols Stimulate IL-1 beta Secretion of Macrophage through TLRs/MyD88/NF-kappa B Pathway and NLRP3 Inflammasome Activation".SMALL 10.12(2014):2362-2372.
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