Asbestos induces inflammatory cytokines in the lung through redox sensitive transcription factors

Our plain-English summary of Asbestos induces inflammatory cytokines in the lung through redox sensitive transcription factors, by M.I. Luster, P.P. Simeonova (Toxicology Letters, 1998).

The study

• Authors: M.I. Luster, P.P. Simeonova
• Journal: Toxicology Letters
• Published: 1998;102-103:271-5
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Studies are summarized demonstrating that the inflammatory cytokines, interleukin IL-6 and IL-8, play a direct role in asbestos lung diseases and are produced by lung epithelial cells in direct response to the fibers. This response is controlled by changes in the cellular oxidative/state induced by iron present in the fiber through Fenton-type chemistry. As a result of this oxidative stress, the redox sensitive transcription factors, NF-kappaB and NF-IL-6, which help regulate cytokine gene expression, are activated.

In plain English

This short report, from researchers at the US National Institute for Occupational Safety and Health, reviewed the authors' own laboratory studies of how asbestos fibers make lung cells release inflammatory signaling proteins (cytokines). No people or animals were studied. The experiments used human lung lining (epithelial) cells grown in culture, the A549 cell line, which originally came from a person with lung cancer. The cells were exposed to crocidolite asbestos from South Africa. Crocidolite produced a dose-related rise in the cytokines IL-8 and IL-6, and IL-8 rose more strongly. Cell damage at the higher dose was minimal. Chemicals that remove hydroxyl radicals, a reactive form of oxygen, reduced cytokine release: completely with one agent (TMTU) and partly with another (DMTU). Hydrogen peroxide alone also raised IL-6. Asbestos increased binding of the transcription factor NF-kappaB to a control region of the IL-6 gene, and TMTU cut that binding by 50%. The authors concluded that asbestos induces these cytokines in lung epithelial cells through reactive oxygen produced by iron-dependent chemistry. They also cited their earlier work for this conclusion.

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: Review of the authors' own previously published laboratory (cell culture) experiments
• Who was studied: No human subjects or animals. A549 human type II-like pulmonary epithelial cells (originally derived from an individual with alveolar cell carcinoma, purchased from the American Type Culture Collection). Normal human bronchoepithelial (NHBE) cells were also purchased, but no results for them are presented.
• Exposure: Crocidolite asbestos (sample ML-6) from a mine in the Kuruman Hills of the Kalahari desert, South Africa, added to cell cultures at a range of concentrations (units garbled in the scanned text). Hydrogen peroxide was tested for comparison.
• Main results:
  • In A549 cells, crocidolite produced a concentration-dependent increase in secretion of IL-8 and IL-6.
  • The increase in IL-8 was significantly more vigorous than the increase in IL-6.
  • Cell damage (LDH leakage) occurred at the higher asbestos concentration but was minimal compared with maximal LDH release (data not shown).
  • Intracellular hydroxyl radical scavengers significantly decreased asbestos-induced IL-8 and IL-6 secretion, ranging from complete inhibition with TMTU to partial inhibition with DMTU.
  • Adding hydrogen peroxide directly to A549 cells dose-dependently stimulated IL-6 secretion, and TMTU abolished this response (data not shown).
  • Asbestos increased nuclear protein binding to the NF-kappaB binding site in the IL-6 gene promoter. The bound complex contained the p50 and p65 subunits of NF-kappaB.
  • TMTU decreased asbestos-stimulated DNA binding activity by 50% and hydrogen peroxide-stimulated binding by 70%. The authors said this suggests redox dependency.
• The authors' conclusion: The authors concluded that asbestos readily induces secretion of inflammatory cytokines in lung epithelial cells through generation of reactive oxygen species via iron-dependent Fenton chemistry. They stated that cytokine expression parallels activation of the redox-sensitive transcription factors NF-kappaB and NF-IL-6, citing their earlier studies for this.

Topics

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

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