Involvement of IL-1 genes in the cellular responses to carbon nanotube exposure

Our plain-English summary of Involvement of IL-1 genes in the cellular responses to carbon nanotube exposure, by Y.J. Arnoldussen, A. Skogstad, V. Skaug, et al (Cytokine, 2015).

The study

• Authors: Y.J. Arnoldussen, A. Skogstad, V. Skaug, M. Kasem, A. Haugen, N. Benker, S. Weinbruch, R.N. Apte, S. Zienolddiny
• Journal: Cytokine
• Published: 2015;73(1):128-37
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The interleukin-1 (IL-1) family has been implicated in cellular responses to nanoparticles including carbon nanotubes (CNTs). IL-1α and β are key proinflammatory cytokines important in inflammatory and oxidative stress responses. The aim of this study was to characterize the role of IL-1 in cellular responses of CNTs in cells from IL-1α/β wild type (IL1-WT) mice and cells with reduced inflammatory potential from IL-1α/β deficient (IL1-KO) mice. Two multi-walled CNTs, CNT-1 containing long and thick fibers and CNT-2 containing short and thin fibers, were compared to UICC crocidolite asbestos fibers. Upon CNT exposure toxicity and apoptosis were affected differently in IL1-WT and IL1-KO cells. Upregulation of TNFα and IL-1α mRNA expression in IL1-WT cells was dependent on the type of CNT. On the contrary precursor IL-1α protein was downregulated after 24h. The mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK) was activated in IL1-KO cells and regulated by CNTs, whereas no significant changes of extracellular regulated kinase (ERK) were observed when comparing IL1-WT and IL1-KO cells. In summary, the results presented here indicate that IL-1 contributes to the cellular and molecular effects of CNT exposure and that the type of CNT has an important effect on the cellular response.

Copyright © 2015 Elsevier Ltd. All rights reserved.

In plain English

This was a laboratory study on cells, not on people or whole animals. The authors used two mouse tumor cell lines. One had normal interleukin-1 genes (IL-1α and IL-1β, which help drive inflammation). In the other, both genes were knocked out. The cells were exposed to two multi-walled carbon nanotubes and, for comparison, to UICC crocidolite asbestos. CNT-1 had long, thick fibers; CNT-2 had short, thin fibers. Measured by number of fibers, the knockout cells survived significantly better than the normal cells after 24 hours, for both nanotubes and for asbestos. At 48 hours the normal cells survived better, but only with CNT-2. Cell death depended on the nanotube type. After 48 hours at 10 micrograms per milliliter of CNT-1, 7.1% of knockout cells were dying by apoptosis, compared with 1.9% of normal cells. The authors concluded that IL-1 may make cells more sensitive to the toxic effects of nanotubes, and that these effects depend strongly on the type of nanotube. They stated that their findings need checking in animals.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro (cell culture) laboratory experiment comparing IL-1-normal and IL-1-knockout mouse cells exposed to carbon nanotubes and asbestos
• Who was studied: Two mouse fibrosarcoma cell lines, derived from 3-methylcholanthrene-induced tumors in BALB/c mice. One line had normal IL-1α/β genes (IL1-WT); the other had both IL-1α and IL-1β knocked out (IL1-KO).
• Exposure: Two multi-walled carbon nanotubes: CNT-1 (Mitsui-7, long and thick fibers) and CNT-2 (made by arc discharge, short and thin fibers). They were compared with UICC crocidolite asbestos. The main experiments used 5 and 10 micrograms per milliliter of each nanotube and 20 micrograms per milliliter of asbestos, for 24 and 48 hours.
• Main results:
  • The two nanotubes differed in form. Single fibers made up 54% of fibrous objects in CNT-1 and nearly 90% in CNT-2. Electron microscope analysis found only carbon in both nanotubes.
  • When survival was measured against fiber number, IL1-KO cells exposed to the nanotubes and to asbestos had significantly higher survival than IL1-WT cells after 24 hours.
  • At 48 hours this reversed: IL1-WT cells showed higher survival, but only with CNT-2.
  • Without any exposure, IL1-KO cells had a significantly lower percentage of cells undergoing apoptosis than IL1-WT cells.
  • The highest apoptosis level was 7.1%, in IL1-KO cells after 10 micrograms per milliliter of CNT-1 for 48 hours. IL1-WT cells given the same dose had 1.9%.
  • With CNT-2, IL1-KO cells had significantly lower apoptosis than IL1-WT cells at both doses and both time points.
  • TNFα messenger RNA was absent in IL1-KO cells. In IL1-WT cells, CNT-1 increased it by about 1.5-fold at 24 hours and 3-fold at 48 hours, at both doses.
  • In IL1-WT cells, CNT-2 significantly increased TNFα messenger RNA by 1.5-fold after 48 hours, similar to the effect of asbestos.
  • In IL1-WT cells, CNT-1 and asbestos each raised IL-1α messenger RNA about 1.5-fold at 24 hours. IL-1β expression in IL1-WT cells decreased significantly at 24 hours.
  • The precursor form of IL-1α protein in IL1-WT cells fell significantly at 24 hours with CNT-1 and with asbestos. Release of TNFα, IL-1α and IL-1β into the culture medium was not detected.
  • IL1-KO cells had significantly higher activation (phosphorylation) of the signaling protein JNK than IL1-WT cells, whether or not they were exposed. The signaling protein ERK did not show this difference.
• The authors' conclusion: The authors concluded that IL-1 may be involved in making cells more sensitive to the toxic effects of carbon nanotubes. They added that these effects depend strongly on the type of nanotube.
• Limitations the authors state:
  • The findings come from cells in culture and, the authors state, need to be verified in animal experiments.
  • IL-1β protein could not be measured because no working antibody was available.
  • IL-1β expression might change at earlier or later time points than the ones tested.
  • Cytokines can stick to particles, so removing the particles before the ELISA test may have removed the cytokines being measured.
  • CNT-2 fibers may be thinner than the scanning electron microscope can detect.
  • Other batches of CNT-1 have been reported to contain low levels of nickel or iron.

Topics

Medical terms in this study, explained in our Lexicon: Cytokine, Oxidative Stress, UICC, Crocidolite, Apoptosis.

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