Interleukin-1-mediated release of interleukin-8 by asbestos-stimulated human pleural mesothelial cells

Our plain-English summary of Interleukin-1-mediated release of interleukin-8 by asbestos-stimulated human pleural mesothelial cells, by D.E. Griffith, E.J. Miller, L.D. Gray, et al (American Journal of Respiratory Cell and Molecular Biology, 1994).

The study

• Authors: D.E. Griffith, E.J. Miller, L.D. Gray, S. Idell, A.R. Johnson
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1994;10(3):245-52
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The pleuropulmonary response to inhaled asbestos frequently involves inflammation and release of various cytokines from lung cells. Among these, interleukin-8 (IL-8) released from the mesothelium could augment inflammation of the pleura by attracting neutrophils to the pleural space. We used cultures of human pleural mesothelial cells (HPMC) to examine the mechanism of IL-8 production by asbestos and cytokines. Suspensions of amosite, chrysotile, or crocidolite asbestos in concentrations as low as 5 micrograms/ml enhanced release of IL-8 from HPMC during 6 h of incubation at 37 degrees C. Electron microscopy of asbestos-treated HPMC showed that the cells avidly engulfed each of the different types of asbestos fibers. Two proinflammatory cytokines, interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha, enhanced IL-8 release within 2 h and had an even greater effect after 6 h. Release of IL-8 was measured by an enzyme-linked immunosorbent assay, and functional activity of the cytokine was assessed by chemotaxis of human neutrophils. Identity of IL-8 in HPMC supernatants was established by absorption with an antibody to IL-8. Preincubation of HPMC with IL-1 receptor antagonist (IL-1ra) significantly decreased release of IL-8 after stimulation with amosite or crocidolite asbestos. We conclude that HPMC release IL-8 in response to asbestos stimulation and that the response is, in part, mediated by IL-1, mainly in the form of IL-1 alpha.

In plain English

This was a laboratory study of human pleural mesothelial cells, the cells that line the chest cavity. The cells were grown from pleural fluid taken from eight hospital patients with lung cancer in Tyler, Texas. The authors exposed the cells to amosite, chrysotile or crocidolite asbestos at 5, 10 and 25 micrograms per milliliter, and to two inflammatory signaling proteins, IL-1 and TNF-alpha. They then measured release of IL-8, a protein that attracts white blood cells called neutrophils. After 2 hours, amosite and crocidolite had not raised IL-8 above basal levels. After 6 hours, all three asbestos types raised IL-8 release to 200 to 300% of basal levels. The cells engulfed every fiber type. Crocidolite-exposed cells released IL-1 alpha in 12 of 16 samples. A blocker of IL-1 blunted IL-8 release after amosite or crocidolite exposure. The authors concluded that these cells release IL-8 in response to asbestos, and that the response is partly mediated by IL-1, mainly IL-1 alpha. They noted the release might partly be a nonspecific response to particles.

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: Laboratory (in vitro) experiment on cultured human pleural mesothelial cells
• Who was studied: Mesothelial cells grown from pleural fluid of eight subjects with lung cancer. The fluid was collected by thoracentesis done for clinical reasons from hospitalized patients at the University of Texas Health Center, Tyler, Texas. None of the subjects had evidence of infection.
• Exposure: Amosite, chrysotile or crocidolite asbestos at final concentrations of 5, 10 and 25 micrograms per milliliter, for 2 to 6 hours. Woolastinite (as the article spells it) at 10 and 25 micrograms per milliliter was the nonfiber particle control. The cytokines were IL-1 alpha (2.5 and 5 ng/ml) and TNF-alpha (50 and 100 ng/ml).
• Main results:
  • In unstimulated cells, basal IL-8 release over 6 hours ranged from 2 to 10 ng/ml.
  • Cells given IL-1 or TNF-alpha raised IL-8 release to about 150% of basal over 2 hours, and to as much as 300% of basal by 6 hours (P less than 0.001).
  • In cells exposed to amosite or crocidolite, IL-8 did not exceed basal levels after 2 hours. After 6 hours, asbestos-treated cells released significantly more IL-8 than control cells (P less than 0.001).
  • All three asbestos types raised IL-8 release to 200 to 300% of basal levels. For amosite and crocidolite, the amount was not related to concentration. For chrysotile, the highest concentration released more IL-8 than the low or intermediate concentrations (P less than 0.01).
  • Amosite and crocidolite were cytotoxic at the highest concentration, measured as percent chromium-51 release. Amosite was 14 at 25 micrograms per milliliter versus 4 in controls. Crocidolite was 20 at 25 micrograms per milliliter versus 5 in controls. Chrysotile was 8 at 25 micrograms per milliliter versus 7 in controls.
  • Woolastinite increased IL-8 only at 25 micrograms per milliliter, by approximately 25% compared with control cells. This difference was marginally significant (P less than 0.05).
  • In media from cells exposed to 10 micrograms per milliliter of crocidolite, 12 of 16 samples were positive for IL-1 alpha (P less than 0.001) and 6 of 16 were positive for IL-1 beta (P less than 0.066). TNF-alpha was below the assay's detection level in both control and asbestos-treated cells.
  • When media from amosite- or crocidolite-treated cells were passed through an anti-IL-8 antibody column, less than 5% of the cytokine remained, and chemotactic activity for neutrophils was significantly reduced (P less than 0.004).
  • Pretreating cells with 10 ng/ml of IL-1 receptor antagonist blunted the IL-8 response to amosite or crocidolite fibers at 10 micrograms per milliliter (P less than 0.01).
  • The cells engulfed asbestos fibers of every type: more than one third of treated cells contained fibers. Many cells, especially those exposed to crocidolite, accumulated multiple fibers.
• The authors' conclusion: The authors concluded that human pleural mesothelial cells release IL-8 in response to asbestos stimulation, and that the response is in part mediated by IL-1, mainly in the form of IL-1 alpha.
• Limitations the authors state:
  • The authors noted that IL-8 release by asbestos-stimulated cells might be, in part, a nonspecific response to contact with particles.
  • The authors noted that contact with culture plates induces IL-8 release in monocytes, which might account for the basal IL-8 release seen in untreated cells.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Inflammation, Cytokine, Mesothelium, Pleura, Amosite, Chrysotile, Crocidolite.

Related studies

• Asbestos fibers and interleukin-1 upregulate the formation of reactive nitrogen species in rat pleural mesothelial cells — N. Choe, S. Tanaka, et al. (1998)
• Pleural mesothelial cells stimulated by asbestos release chemotactic activity for neutrophils in vitro — V.B. Antony, C.L. Owen, et al. (1989)
• Evidence of a role for mesothelial cell-derived interleukin 8 in the pathogenesis of asbestos-induced pleurisy in rabbits — A.M. Boylan, C. Rüegg, et al. (1992)
• Relative release of interleukin-1 beta and interleukin-1 receptor antagonist by alveolar macrophages. A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis — J.N. Kline, D.A. Schwartz, et al. (1993)
• Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation — H. Yang, Z. Rivera, et al. (2010)
• Effects of asbestos and man-made vitreous fibers on cell division in cultured human mesothelial cells in comparison to rodent cells — K. Pelin, P. Kivipensas, et al. (1995)

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