| Autor: |
Arnoldussen YJ; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway., Skaug V; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway., Aleksandersen M; b Department of Basic Sciences and Aquatic Medicine , Faculty of Veterinary Medicine, Norwegian University of Life Sciences , Oslo , Norway., Ropstad E; c Department of Production Animal Clinical Sciences , Faculty of Veterinary Medicine, Norwegian University of Life Sciences , Oslo , Norway., Anmarkrud KH; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway., Einarsdottir E; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway., Chin-Lin F; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway., Granum Bjørklund C; c Department of Production Animal Clinical Sciences , Faculty of Veterinary Medicine, Norwegian University of Life Sciences , Oslo , Norway., Kasem M; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway., Eilertsen E; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway., Apte RN; d The Shraga Segal Department of Microbiology, Immunology, and Genetics, The Faculty of Health Sciences , Ben Gurion University of the Negev , Beer Sheva , Israel., Zienolddiny S; a Department of Biological and Chemical Work Environment , National Institute of Occupational Health , Oslo , Norway. |
| Abstrakt: |
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. |
