Combined effect of cigarette smoke and mineral fibers on the gene expression of cytokine mRNA

Our plain-English summary of Combined effect of cigarette smoke and mineral fibers on the gene expression of cytokine mRNA, by Y. Morimoto, T. Tsuda, H. Hori, et al (Environmental Health Perspectives, 1999).

The study

• Authors: Y. Morimoto, T. Tsuda, H. Hori, H. Yamato, A. Ohgami, T. Higashi, N. Nagata, M. Kido, I. Tanaka
• Journal: Environmental Health Perspectives
• Published: 1999;107(6):495-500
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

To investigate which parameters are stimulated by mineral fibers and whether cigarette smoke enhanced a fiber-induced response, we examined the level of cytokine mRNA from alveolar macrophages (AMs) and lungs of rats exposed to mineral fibers and cigarette smoke in vivo. Male Wistar rats were given a single intratracheal instillation of 2 mg of Union Internationale Contre le Cancer chrysotile or refractory ceramic fiber (RF1). The animals then inhaled a side stream of smoke 5 days per week for 4 weeks. The expression of manganese superoxide dismutase, inducible nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF), interleukin-1[alpha] (IL-1[alpha]), interleukin-6 (IL-6), and tumor necrosis factor-[alpha] (TNF[alpha]) mRNA from lipopolysaccharide-stimulated AMs and lungs of rats exposed to mineral fibers and/or cigarette smoke were assessed using semiquantitative reverse-transcriptase polymerase chain reaction. Exposure only to cigarette smoke increased in IL-1[alpha] mRNA levels in AMs. Chrysotile stimulated the expression of IL-1[alpha], TNF[alpha], and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1[alpha] and TNF[alpha] in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile; IL-1[alpha] in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1[alpha], iNOS, and bFGF were increased in rats stimulated with mineral fibers, and the stimulating effects of mineral fibers were enhanced by cigarette smoke. Therefore, IL-1[alpha], iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers.

In plain English

This was a rat experiment, not a human study. The authors split 30 male Wistar rats into six groups. Each rat received one dose into the windpipe: saline as a control, or 2 mg of chrysotile asbestos or a refractory ceramic fiber, RF1. Some rats then breathed cigarette smoke 4 hours a day, 5 days a week, for 4 weeks. The authors measured inflammation-related gene activity (messenger RNA) in lung tissue and in lung lavage cells (alveolar macrophages), after stimulating these cells in culture with lipopolysaccharide. In macrophages, IL-1 alpha rose significantly in every exposed group compared with saline. TNF alpha rose with chrysotile or RF1 but not with smoke alone. IL-6 rose with chrysotile alone, and iNOS rose only with fibers plus smoke. In lung tissue, chrysotile raised TNF alpha and bFGF. Combined fiber and smoke exposure had a significant effect on bFGF, and chrysotile plus smoke had what the authors called a synergistic effect on IL-6. Mn-SOD did not change significantly. The authors concluded that IL-1 alpha, iNOS and bFGF were possible markers of fiber-induced lung remodeling.

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. Rats were given fibers into the windpipe, with or without cigarette smoke inhalation. Gene activity (mRNA) was then measured by semiquantitative RT-PCR in lung tissue and in alveolar macrophages that had been stimulated in culture with lipopolysaccharide.
• Who was studied: 30 male Wistar rats, 10 weeks old, divided into six groups: saline, chrysotile, RF1, cigarette smoke, chrysotile + cigarette smoke, and RF1 + cigarette smoke. The number per group is not stated separately. The laboratory was at the University of Occupational and Environmental Health, Japan.
• Exposure: Rats received a single intratracheal instillation of saline, or of chrysotile or RF1 fiber suspension at 2 mg in 0.2 mL. The chrysotile was Union Internationale Contre le Cancer chrysotile; RF1 was an alumina silicate ceramic fiber. Smoke from 20 cigarettes was given 4 hours a day, 5 days a week, for 4 weeks, at a mass concentration of 10 mg/m3. Chrysotile fibers had a geometric mean diameter of 0.085 micrometers and a length of 0.7 micrometers. RF1 fibers had a diameter of 0.77 micrometers and a length of 12.0 micrometers.
• Main results:
  • Total cells recovered by lung lavage (times 10 to the 5th) were higher in exposed groups than in controls: control 4.4, cigarette 6.4, chrysotile 5.6, RF1 5.5, chrysotile + cigarette smoke 5.7, RF1 + cigarette smoke 9.1.
  • IL-1 alpha mRNA in alveolar macrophages increased significantly compared with saline in all five exposed groups. It was highest in the RF1 + smoke group, but that level was not significantly different from smoke alone or RF1 alone. IL-1 alpha was not raised in lung tissue.
  • TNF alpha mRNA in macrophages increased significantly in chrysotile- or RF1-exposed rats compared with controls, but not in smoke-exposed rats. There was no combined fiber and smoke effect on TNF alpha in macrophages. In lung tissue, TNF alpha was increased with chrysotile; the increase with RF1 was not significant.
  • IL-6 mRNA in macrophages increased with chrysotile alone. In lung tissue, chrysotile plus cigarette smoke had a synergistic effect on IL-6, although neither exposure alone raised it.
  • iNOS mRNA in macrophages was not increased by smoke or fibers alone. It increased significantly compared with controls in rats given fibers plus smoke. In lung tissue, iNOS fell markedly in smoke-exposed rats.
  • Mn-SOD mRNA showed no significant changes in macrophages or lungs in any group.
  • bFGF mRNA was not detected in macrophages. In lung tissue it increased with chrysotile, but not with smoke or RF1 alone. The combined effect of fibers and smoke on bFGF was significant.
  • Under the microscope, foreign body giant cells and mononuclear cells around bronchioles were seen only in the chrysotile and chrysotile + smoke groups. The authors described these lungs as without a fibrotic form. No definite changes were seen in the other four groups.
• The authors' conclusion: The authors concluded that IL-1 alpha, iNOS and bFGF mRNA were increased by mineral fibers and enhanced by combined exposure to fibers and cigarette smoke. They suggested these would be possible parameters (markers) of lung remodeling induced by mineral fibers.
• Limitations the authors state:
  • The authors suggested that Mn-SOD mRNA levels may have peaked earlier and returned to normal, because the recovery time was 4 weeks.

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Cytokine, Alveolar Macrophage, Chrysotile, Superoxide, Inducible Nitric Oxide Synthase (iNOS), Fibroblast, Necrosis.

Related studies

• Synergistic effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor by alveolar macrophages of rats — Y. Morimoto, M. Kido, et al. (1993)
• Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke — X.D. Wang, C. Liu, et al. (1999)
• Cigarette smoke increases the penetration of asbestos fibers into airway walls — D. McFadden, J. Wright, et al. (1986)
• Effects of cigarette smoke and asbestos on airway, vascular and mesothelial cell proliferation — H. Sekhon, J. Wright, et al. (1995)
• Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig — V. Tron, J.L. Wright, et al. (1987)
• Cigarette smoke, asbestos, and small irregular opacities — W. Weiss (1984)

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