Long-lasting production of TGF-beta1 by alveolar macrophages exposed to low doses of asbestos without apoptosis

Our plain-English summary of Long-lasting production of TGF-beta1 by alveolar macrophages exposed to low doses of asbestos without apoptosis, by Y. Nishimura, T. Nishiike-Wada, Y. Wada, et al (International Journal of Immunopathology and Pharmacology, 2007).

The study

• Authors: Y. Nishimura, T. Nishiike-Wada, Y. Wada, Y. Miura, T. Otsuki, H. Iguchi
• Journal: International Journal of Immunopathology and Pharmacology
• Published: 2007;20(4):661-71
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-alpha, which induces the production of TGF-beta1, leading to lung fibrogenesis. The present study examines the production of TGF-beta1 by AMs exposed to chrysotile B asbestos (CH) in vivo or in vitro and the relationship between TGF-beta1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-alpha, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) 1 day after the instillation, followed by increases in TGF-beta1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-beta1 in culture compared to those from the control rats. The addition of 2.5 mug/cm2 of CH augmented the production of TGF-beta1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 microg/cm2 of CH, but was drastically induced at over 12.5 microg/cm2. In contrast, the production of TGF-beta1 by AMs peaked at around 2.5 microg/cm2 of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xL increased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-beta1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-beta1 may contribute not only to lung fibrosis but also to immune suppression.

In plain English

This was a laboratory study in rats and in cultured rat lung cells. The authors put 4 mg of chrysotile B asbestos, or saline for comparison, into the windpipes of male Wistar rats and washed out their lungs 1 or 5 days later. They also exposed alveolar macrophages, immune cells taken from the lungs, to chrysotile in culture dishes at doses from 1.25 to 25 µg/cm². One day after instillation, the rats' lung fluid showed significant increases in the inflammatory signals TNF-α, IL-1β and IL-6. At 5 days it showed significantly more TGF-β1 and more apoptotic (dying) cells. In culture, 12.5 µg/cm² quickly triggered apoptosis of macrophages, while 2.5 µg/cm² caused no significant increase. TGF-β1 production peaked at around 2.5 µg/cm² and stayed high at 1.25 to 2.5 µg/cm² from day 8 to day 11. Exposed cells showed more of the survival proteins Bcl-2 and Bcl-xL. The authors concluded that these macrophages could, on their own, gain an increased ability to produce TGF-β1 and survive without drastic apoptosis under low-dose, but not high-dose, chrysotile exposure.

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: animal experiment (intratracheal instillation in rats) combined with in vitro cell-culture experiments on alveolar macrophages
• Who was studied: Male Wistar rats (number not stated) and alveolar macrophages recovered from their bronchoalveolar lavage fluid; experiments conducted at Hyogo College of Medicine, Japan; study dates not given
• Exposure: Chrysotile B (UICC standard reference material): 4 mg instilled via the trachea in rats; in culture, doses from 1.25 to 25 µg/cm²
• Main results:
  • In lung lavage fluid from chrysotile-instilled rats 1 day after instillation, TNF-α, IL-1β and IL-6 were significantly increased compared with saline-instilled rats
  • TGF-β1 was not increased in lavage fluid at 24 hours, but was significantly increased at 5 days after chrysotile instillation
  • At 5 days, all three measures of apoptotic cells were significantly higher in lavage fluid from chrysotile-instilled rats than from saline-instilled rats
  • Macrophages from chrysotile-instilled rats produced significantly more TGF-β1 in culture than those from saline-instilled rats when not exposed to chrysotile in vitro
  • With 2.5 µg/cm² chrysotile added in vitro, macrophages from saline-instilled and chrysotile-instilled rats produced similarly high amounts of TGF-β1
  • In cultured macrophages, 12.5 µg/cm² chrysotile immediately induced apoptosis
  • At 2.5 µg/cm² chrysotile, apoptosis of cultured macrophages was slight and not significantly different from control cultures
  • At 25 µg/cm² chrysotile, total annexin V-positive (apoptotic) macrophages exceeded 65%
  • TGF-β1 production by cultured macrophages after 5 days significantly increased and peaked at around 2.5 µg/cm² chrysotile, and did not increase above 5 µg/cm²
  • Macrophages exposed to 1.25 to 2.5 µg/cm² chrysotile showed a higher level of TGF-β1 production during days 8 to 11 of culture
  • Macrophages exposed to 2.5 µg/cm² chrysotile showed increased Bcl-2 and Bcl-xL, with a larger increase for Bcl-xL; surviving macrophages at 12.5 µg/cm² also showed increased levels
• The authors' conclusion: The authors concluded that alveolar macrophages can autonomously acquire an increased ability to produce TGF-β1 and survive without drastic apoptosis under low-dose, but not high-dose, chrysotile exposure
• Limitations the authors state:
  • The authors noted that their findings do not rule out a fibrogenic role for apoptotic cells induced by high doses of asbestos

Topics

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

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Apoptosis, Chrysotile, Bronchoalveolar Lavage (BAL), Fibrosis.

Related studies

• Asbestos induces apoptosis in human alveolar macrophages — R.F. Hamilton, L.L. Iyer, et al. (1996)
• Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats — I.Y. Adamson, H. Prieditis, et al. (1997)
• Nitric oxide (NO) synthase activity in the lung and NO synthesis in alveolar macrophages of rats increased on exposure to asbestos — H. Iguchi, S. Kojo, et al. (1996)
• Bidirectional modulation of TNF-alpha production by alveolar macrophages in asbestos-induced pulmonary fibrosis — S. Ouellet, H. Yang, et al. (1993)
• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)
• Involvement of the ICE family of proteases in silica-induced apoptosis in human alveolar macrophages — R. Iyer, A. Holian (1997)

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