Atomic Layer Deposition Coating of Carbon Nanotubes with Aluminum Oxide Alters Pro-Fibrogenic Cytokine Expression by Human Mononuclear Phagocytes In Vitro and Reduces Lung Fibrosis in Mice In Vivo

作者：Taylor Alexia J; McClure Christina D; Shipkowski Kelly A; Thompson Elizabeth A; Hussain Salik; Garantziotis Stavros; Parsons Gregory N; Bonner James C^*

来源：PLos One, 2014, 9(9): e106870.

DOI：10.1371/journal.pone.0106870

Background: Multi-walled carbon nanotubes (MWCNTs) pose a possible human health risk for lung disease as a result of inhalation exposure. Mice exposed to MWCNTs develop pulmonary fibrosis. Lung macrophages engulf MWCNTs and produce pro-fibrogenic cytokines including interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and osteopontin (OPN). Atomic layer deposition (ALD) is a novel process used to enhance functional properties of MWCNTs, yet the consequence of ALD-modified MWCNTs on macrophage biology and fibrosis is unknown. %26lt;br%26gt;Methods: The purpose of this study was to determine whether ALD coating with aluminum oxide (Al2O3) would alter the fibrogenic response to MWCNTs and whether cytokine expression in human macrophage/monocytes exposed to MWCNTs in vitro would predict the severity of lung fibrosis in mice. Uncoated (U)-MWCNTs or ALD-coated (A)-MWCNTs were incubated with THP-1 macrophages or human peripheral blood mononuclear cells (PBMC) and cell supernatants assayed for cytokines by ELISA. C57BL6 mice were exposed to a single dose of A- or U-MWCNTs by oropharyngeal aspiration (4 mg/kg) followed by evaluation of histopathology, lung inflammatory cell counts, and cytokine levels at day 1 and 28 post-exposure. %26lt;br%26gt;Results: ALD coating of MWCNTs with Al2O3 enhanced IL-1 beta secretion by THP-1 and PBMC in vitro, yet reduced protein levels of IL-6, TNF-alpha, and OPN production by THP-1 cells. Moreover, Al2O3 nanoparticles, but not carbon black NPs, increased IL-1 beta but decreased OPN and IL-6 in THP-1 and PBMC. Mice exposed to U-MWCNT had increased levels of all four cytokines assayed and developed pulmonary fibrosis by 28 days, whereas ALD-coating significantly reduced fibrosis and cytokine levels at the mRNA or protein level. %26lt;br%26gt;Conclusion: These findings indicate that ALD thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-alpha, and OPN, but not IL-1 beta, predict MWCNT-induced fibrosis in the lungs of mice in vivo.

• 出版日期2014-9-12