Inflammation in the pleural cavity following injection of multi-walled carbon nanotubes is dependent on their characteristics and the presence of IL-1 genes

Yke Jildouw Arnoldussen, Vidar Skaug, Mona Aleksandersen, Erik Ropstad, Kristine Haugen Anmarkrud, Elin Einarsdottir, Fang Chin-Lin, Cesilie Granum Bjørklund, Mayes Kasem, Einar Eilertsen, Ron N. Apte, Shanbeh Zienolddiny

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Upon inhalation, multi-walled carbon nanotubes (MWCNTs) may reach the subpleura and pleural spaces, and induce pleural inflammation and/or mesothelioma in humans. However, the mechanisms of MWCNT-induced pathology after direct intrapleural injections are still only partly elucidated. In particular, a role of the proinflammatory interleukin-1 (IL-1) cytokines in pleural inflammation has so far not been published. We examined the MWCNT-induced pleural inflammation, gene expression abnormalities, and the modifying role of IL-1α and β cytokines following intrapleural injection of two types of MWCNTs (CNT-1 and CNT-2) compared with crocidolite asbestos in IL-1 wild-type (WT) and IL-1α/β KO (IL1-KO) mice. Histopathological examination of the pleura 28 days post-exposure revealed mesothelial cell hyperplasia, leukocyte infiltration, and fibrosis occurring in the CNT-1 (Mitsui-7)-exposed group. The pleura of these mice also showed the greatest changes in mRNA and miRNA expression levels, closely followed by CNT-2. In addition, the CNT-1-exposed group also presented the greatest infiltrations of leukocytes and proliferation of fibrous tissue. WT mice were more prone to development of sustained inflammation and fibrosis than IL1-KO mice. Prominent differences in genetic and epigenetic changes were also observed between the two genotypes. In conclusion, the fibrotic response to MWCNTs in the pleura depends on the particles’ physico-chemical properties and on the presence or absence of the IL-1 genes. Furthermore, we found that CNT-1 was the most potent inducer of inflammatory responses, followed by CNT-2 and crocidolite asbestos.

Original languageEnglish
Pages (from-to)522-538
Number of pages17
JournalNanotoxicology
Volume12
Issue number6
DOIs
StatePublished - 3 Jul 2018

Keywords

  • IL-1
  • MWCNT
  • Pleura
  • asbestos
  • in vivo
  • inflammation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

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