Inhibition of inflammatory arthritis using fullerene nanomaterials.
Inhibition of inflammatory arthritis using fullerene nanomaterials.
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DOI：
10.1371/journal.pone.0126290
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kepley CL
中科院分区：
文献类型：
--
作者：
Dellinger AL;Cunin P;Lee D;Kung AL;Brooks DB;Zhou Z;Nigrovic PA;Kepley CL
炎症性关节炎（例如类风湿性关节炎; RA）是一种由多种细胞谱系相互作用驱动的复杂疾病。富勒烯衍生物先前已显示出具有抗炎能力，部分地通过它们阻止肥大细胞（MC）释放炎性介质的能力来介导。认识到MC可以作为炎症性关节炎中自身抗体、可溶性介质和其他效应物群体之间的细胞联系，假设富勒烯衍生物可以用于靶向这种炎症性疾病。测试了一组富勒烯衍生物影响人皮肤来源的MC以及与关节炎、滑膜成纤维细胞和破骨细胞有关的其他谱系的功能的能力。研究表明，某些富勒烯衍生物可阻断MC释放FcγR和TNF-α诱导的介质; RA滑膜成纤维细胞释放TNF-α诱导的介质;以及人破骨细胞的成熟。富勒烯衍生物通过降低线粒体膜电位和Fcγ R介导的细胞活性氧和NF-κB活化的增加来介导MC抑制。基于这些体外数据，选择两种富勒烯衍生物（ALM和TGA）用于在C57 BL/6小鼠中使用K/BxN血清转移关节炎和在DBA/1小鼠中使用胶原诱导的关节炎（CIA）的体内研究。染料共轭富勒烯证实本地化受影响的关节炎动物，但不是在健康对照。在K/BxN模型中，富勒烯减轻了关节炎，这种作用伴随着组织学炎症、软骨/骨侵蚀和血清TNF-α水平的降低。富勒烯仍然能够减弱肥大细胞缺陷小鼠Cre-Master小鼠中的K/BxN关节炎，表明MC以外的谱系代表该系统中的相关靶标。这些研究表明，富勒烯衍生物可能有希望作为评估工具和关节炎的抗炎治疗。
Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC). Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA) were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA) in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.
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影响因子：
64.8
作者：
GORDON, JR;GALLI, SJ
通讯作者：
GALLI, SJ
DOI：
10.1073/pnas.96.8.4524
发表时间：
1999-04-13
影响因子：
11.1
作者：
Haqqi, TM;Anthony, DD;Mukhtar, H
通讯作者：
Mukhtar, H
影响因子：
6.5
作者：
Fumelli, C;Marconi, A;Pincelli, C
通讯作者：
Pincelli, C
DOI：
10.1016/s0006-291x(02)00445-x
发表时间：
2002-05-31
影响因子：
3.1
作者：
Foley, S;Crowley, C;Larroque, C
通讯作者：
Larroque, C
影响因子：
--
作者：
GRUBER, B;POZNANSKY, M;KAPLAN, AP
通讯作者：
KAPLAN, AP