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| Polyhydroxylated Metallofullerenols Stimulate IL-1 beta Secretion of Macrophage through TLRs/MyD88/NF-kappa B Pathway and NLRP3 Inflammasome Activation | |
| Chen, ZY; Liu, Y; Sun, BY; Li, H; Dong, JQ; Zhang, LJ; Wang, LM; Wang, P; Zhao, YL; Chen, CY; chenchy@nanoctr.cn | |
| 2014 | |
| Source Publication | SMALL
 |
| ISSN | 1613-6810 |
| Volume | 10Issue:12Pages:2362—2372 |
| Abstract | 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. |
| Keyword | Nf-kappa-b Mri Contrast Agents Functionalized Fullerene Materials Pattern-recognition Receptors Toll-like Receptors Signaling Pathways Nalp3 Inflammasome Photodynamic Therapy In-vitro Nanoparticles |
| Indexed By | SCI |
| Language | 英语 |
| WOS ID | WOS:000337801200009 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.sinap.ac.cn/handle/331007/14322 |
| Collection | 中科院上海应用物理研究所2011-2020年 |
| Corresponding Author | chenchy@nanoctr.cn |
| Recommended Citation GB/T 7714 | Chen, ZY,Liu, Y,Sun, BY,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 | Chen, ZY.,Liu, Y.,Sun, BY.,Li, H.,Dong, JQ.,...&chenchy@nanoctr.cn.(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 | Chen, ZY,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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