Interdisciplinary Center for Nanotoxicity, Department of Chemistry, Jackson State University, 1400 J. R. Lynch Street, P. O. Box 17910, Jackson, MS 39217, USA.
Nanoscale. 2014 Apr 7;6(7):3488-95. doi: 10.1039/c3nr05772k.
Over the last decade, a great deal of attention has been devoted to study the inflammatory response upon exposure to multi/single-walled carbon nanotubes (CNTs) and different fullerene derivatives. In particular, carbon nanoparticles are reported to provoke substantial inflammation in alveolar and bronchial epithelial cells, epidermal keratinocytes, cultured monocyte-macrophage cells, etc. We suggest a hypothetical model providing the potential mechanistic explanation for immune and inflammatory responses observed upon exposure to carbon nanoparticles. Specifically, we performed a theoretical study to analyze CNT and C60 fullerene interactions with the available X-ray structures of Toll-like receptors (TLRs) homo- and hetero-dimer extracellular domains. This assumption was based on the fact that similar to the known TLR ligands both CNTs and fullerenes induce, in cells, the secretion of certain inflammatory protein mediators, such as interleukins and chemokines. These proteins are observed within inflammation downstream processes resulted from the ligand molecule dependent inhibition or activation of TLR-induced signal transduction. Our computational studies have shown that the internal hydrophobic pockets of some TLRs might be capable of binding small-sized carbon nanostructures (5,5 armchair SWCNTs containing 11 carbon atom layers and C60 fullerene). High binding scores and minor structural alterations induced in TLR ectodomains upon binding C60 and CNTs further supported our hypothesis. Additionally, the proposed hypothesis is strengthened by the indirect experimental findings indicating that CNTs and fullerenes induce an excessive expression of specific cytokines and chemokines (i.e. IL-8 and MCP1).
在过去的十年中，人们已经投入了大量的精力来研究多壁/单壁碳纳米管（CNT）和不同富勒烯衍生物暴露后的炎症反应。特别是，有报道称碳纳米颗粒会在肺泡和支气管上皮细胞、表皮角质形成细胞、培养的单核细胞-巨噬细胞等细胞中引起大量炎症。我们提出了一个假设模型，为暴露于碳纳米颗粒后观察到的免疫和炎症反应提供了潜在的机制解释。具体来说，我们进行了理论研究，以分析 CNT 和 C60 富勒烯与 Toll 样受体（TLR）同源和异源二聚体细胞外结构域的现有 X 射线结构的相互作用。这一假设是基于以下事实，即类似于已知的 TLR 配体，CNTs 和富勒烯都会在细胞中诱导某些炎症蛋白介质（如白细胞介素和趋化因子）的分泌。这些蛋白在炎症下游过程中被观察到，这是由配体分子依赖的 TLR 诱导信号转导的抑制或激活引起的。我们的计算研究表明，一些 TLR 的内部疏水性口袋可能能够结合小尺寸的碳纳米结构（含有 11 个碳原子层的 5,5 扶手椅 SWCNT 和 C60 富勒烯）。C60 和 CNT 结合后，TLR 外结构域的高结合分数和较小的结构改变进一步支持了我们的假设。此外，间接的实验发现也证实了这一假设，即 CNTs 和富勒烯会引起特定细胞因子和趋化因子（即 IL-8 和 MCP1）的过度表达。
