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Comparative study of multiwalled carbon nanotubes and pro-inflammatory IL-1 beta production: The role of purification and surface functionalization

: Lee, H.; Taylor-Just, A.; You, D.; Lison, D.; Brûle, S.; Ziemann, Christina; Creutzenberg, Otto H.; Simon, S.; Vulpoi, A.; Turcu, T.; Bonner, J.C.

The Toxicologist 168 (2019), No.1, Abstract PS 2046
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <58, 2019, Baltimore/Md.>
Fraunhofer ITEM ()

With advancements in nanotechnology, the application of multi-walled carbon nanotubes (MWCNTs) in commercial products has been increasingly expanding. Consequently, increase in exposure of humans to MWCNTs raised questions about potential risks of such materials. The efforts to characterize specific features of MWCNTs that may potentially be associated with adverse health effects have been challenging as variations in the purification process and surface functionalization alter physicochemical properties. As part of the ERA-NET SIINN project ICONS (“International Collaboration On Nanotube Safety”), we examined the consequence of purification, followed by surface functionalization, on MWCNT-induced production of interleukin 1 beta (IL-1 beta) by human macrophages in vitro and in the lungs of mice in vivo. A library of eight differently purified (chemically or thermally) and functionalized (-COOH or -NH2) MWCNT samples were prepared from a single batch of industrially relevant Nanocyl NC7000. THP-1 monocytes were PMA-differentiated to macrophages (40 ng/mL, 48 hrs) and exposed to 1, 10, 100 µg/cm2 MWCNTs. Cell supernatants were analyzed for IL-1 beta via ELISA. Mice (C57BL6 strain, N=4 per group) were exposed via oropharyngeal aspiration to the same library of MWCNTs at doses of 1.6 and 4 mg/kg. After 3 days, BALF was collected and IL-1 beta analyzed via ELISA. THP1 cells exposed to thermally-purified MWCNTs functionalized with -COOH or -NH2 produced more IL-1 beta than when exposed to NC7000. Thermally-purified MWCNTs functionalized with either -COOH or -NH2 produced greater IL-1 beta in the BALF from mice compared to NC7000, whereas chemically purified MWCNTs functionalized with either -COOH or -NH2 produced less IL-1 beta in BALF compared to NC7000. These data suggest that the purification method used prior to surface functionalization is an important determinant in mediating inflammasome activation and IL-1 beta release as part of the innate immune response to MWCNTs. Funding: Supported by NSF Grant 15-022 and NIEHS Training Grant T32ES007046