Diesel exhaust particles stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro,☆☆,,★★

https://doi.org/10.1016/S0091-6749(98)70307-0Get rights and content

Abstract

Background: Epidemiologic and experimental studies suggest that air pollution such as diesel exhaust particles (DEPs), one of the important air pollutants, may play a role in the increasing prevalence of allergic airway diseases. Objective: We studied the effect of suspended particulate matter (SPM) and its main component, DEPs, on the production of IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by human airway epithelial cells in vitro. Methods: SPM obtained from high-volume air samplers and DEPs were added to cultured human nasal polyp–derived upper airway, normal bronchial, and transformed bronchial epithelial cells. Production of GM-CSF and IL-8 by airway epithelial cells was evaluated. Results: Nontoxic doses of DEPs showed a significant stimulatory effect on IL-8 and GM-CSF production by these three kinds of epithelial cells in a dose- and time-dependent fashion. SPM had a stimulatory effect on GM-CSF, but not IL-8, production. These effects were abrogated by treatment with a protein synthesis inhibitor, cycloheximide, suggesting that the process required a de novo protein synthesis. On the double-chamber plates, airway epithelial cells responded to DEPs only when they were stimulated from the apical sides, which can be a model for in vivo environments. Neither charcoal nor graphite showed such stimulatory effects, indicating that the activity of DEPs did not derive from their particulate nature. Benzo(a)pyrene, one of the main aromatic hydrocarbons contained in DEPs, showed a stimulatory effect on the release of the cytokines, and this organic substance might have a causative effect on of the potency of DEPs. Conclusion: We conclude that SPM and DEPs, its main component, might be important air pollutants in the activation of airway epithelial cells for the release of cytokines relevant to allergic airway inflammation. (J Allergy Clin Immunol 1998;101:778-785.)

Section snippets

Preparation of SPM and DEPs

SPM was collected by using a high-volume air sampler (Andersen type, Model AH-600; Sibata Scientific Technology Ltd., Tokyo, Japan). The air sampler was set up at a polluted district in the Tokyo metropolitan area and operated for 6 consecutive days.7 The materials collected during February and March 1987 were pooled and stored at 4° C. The principles of the classification of particles in this instrument were reported previously.16 We used SPM with sizes ranging from 7.0 μm to 10 μm.

The engine

SPM and DEPs stimulated airway epithelial cells to release GM-CSF, IL-8, or both

As shown in Fig. 1, A, SPM at 250 μg/ml had a significant stimulatory effect on GM-CSF release from human upper airway epithelial cells in a time-dependent fashion.

. Effect of SPM on release of GM-CSF by human primary nasal epithelial cells in vitro. Human primary nasal epithelial cells were isolated from resected nasal polyps and cultured in hormonally defined Ham' F12 medium until confluence. A, Cells were treated with and without 250 μg/ml SPM. Supernatants were collected after different time

Discussion

In this report we found that DEPs, one of the important air pollutants, stimulated cytokine production by human airway epithelial cells (Table I).

. Summary of the effect of SPM and DEPs on human airway epithelial cells

PollutantsEpithelial cellsGM-CSF productionIL-8 production
SPMNasal
Bronchial
BEAS-2B
DEPsNasal
Bronchial
BEAS-2B
Benzo(a)pyreneBEAS-2B
The activity was not due to cytotoxicity, and it required a de novo protein synthesis as suggested by the experiment with cycloheximide. The

Acknowledgements

We thank Dr. M. Sagai for his kind supply of DEPs and Ms. Chinami Sakamaki and Asako Hashimoto for their excellent technical support.

References (34)

  • S Takafuji et al.

    Enhancing effect of suspended particulate matter on the IgE antibody production in mice

    Int Arch Allergy Appl Immunol

    (1989)
  • D Diaz-Sanchez et al.

    Diesel exhaust particles induce local IgE production in vivo in humans and alter the pattern of IgE mRNA isoforms

    J Clin Invest

    (1994)
  • M Marini et al.

    Interleukin-1 binds to specific receptors on human bronchial epithelial cells and upregulates granulocyte/macrophage colony-stimulating factor synthesis and release

    Am J Respir Cell Mol Biol

    (1991)
  • TJ Standiford et al.

    Interleukin-8 gene expression by a pulmonary epithelial cell line: a model for cytokine networks in the lung

    J Clin Invest

    (1990)
  • T Ohtoshi et al.

    Monocyte macrophage differentiation induced by human upper airway epithelial cells

    Am J Respir Cell Mol Biol

    (1991)
  • AA. Andersen

    A sampler for respiratory health hazard assessment

    Am Ind Hyg Assoc J

    (1966)
  • J Nakano et al.

    Endotoxin and pro-inflammatory cytokines stimulate endothelin-1 expression and release by airway epithelial cells

    Clin Exp Allergy

    (1994)
  • Cited by (160)

    • Diesel exhaust particle exposure accelerates oxidative DNA damage and cytotoxicity in normal human bronchial epithelial cells through PD-L1

      2023, Environmental Pollution
      Citation Excerpt :

      Many studies have shown that DEPs can increase the expression of genes involved in immune or inflammatory responses, such as cytokines and chemokines, in lung cells (Schwarze et al., 2013). DEPs can significantly increase the production of cytokines such as interleukin (IL)-8 and granulocyte-macrophage colony-stimulating factor in human airway epithelial cells (Ohtoshi et al., 1998). In addition, expression levels of various cytokines such as tumor necrosis factor, IL-6, and monocyte chemoattractant protein-1 are increased in the lungs of mice exposed to DEPs (Saber et al., 2006).

    • Saponin attenuates diesel exhaust particle (DEP)-induced MUC5AC expression and pro-inflammatory cytokine upregulation via TLR4/TRIF/NF-κB signaling pathway in airway epithelium and ovalbumin (OVA)-sensitized mice

      2022, Journal of Ginseng Research
      Citation Excerpt :

      In this study, KRG extracts significantly inhibited DEP-induced expression of the pro-inflammatory cytokines. Since DEP exposure implicated morbid chronic airway pathologies relevant to pro-inflammatory cytokine activation [20], we evaluated the efficacy of KRG as an anti-inflammatory metabolite to alleviate DEP-aggravated inflammation. However, whether ginseng saponin alleviates disease-susceptible inflammatory responses needed more evidence through further studies.

    • The effect of environmental diesel exhaust pollution on SARS-CoV-2 infection: The mechanism of pulmonary ground glass opacity

      2021, Environmental Toxicology and Pharmacology
      Citation Excerpt :

      In response to the dPM2.5 exposure, ACE2 receptor via which SARS-CoV-2 enters the target cells, and the cofactor transmembrane protease serine 2 (TMPRSS2) are highly upregulated in the alveolar epithelial cells (Kim et al., 2020a, 2020b). Importantly, generation and emission of DEPs from diesel engines are one of the main components of aerial PM (Ohtoshi et al., 1998). DEP upregulates adhesion molecules and induces endothelial cell activation.

    • Diesel exhausts particles: Their role in increasing the incidence of asthma. Reviewing the evidence of a causal link

      2019, Science of the Total Environment
      Citation Excerpt :

      ROS formed on the surfaces of particles activate either antioxidant defense mechanisms (at low levels of oxidative stress), inflammatory responses (at intermediate levels of oxidative stress) or cytotoxic effects (at high levels of oxidative stress) (Steiner et al., 2016; Xiao et al., 2003). It is known that DEP increase oxidative stress and influence human bronchial epithelial cell-dendritic cell interactions via cytokines including thymic stromal lymphopoietin (TSLP) (Reibman et al., 2003; Ohtoshi et al., 1998; Boland et al., 1999; Reibman et al., 2002; Bleck et al., 2008; Liu et al., 2007). Bleck et al. (Bleck et al., 2010), using primary culture human bronchial epithelial cells, proposed that DEP-treated cells upregulate Jagged-1 and OX40L in myeloid dendritic cells via TSLP, resulting in functional dendritic cells that support Th2 polarization, although this theory has never been demonstrated in vivo.

    View all citing articles on Scopus

    From athe Departments of Medicine and Physical Therapy and bthe Department of Otolaryngology, University of Tokyo, School of Medicine, Tokyo; and cthe Department of Internal Medicine, University of Teikyo, School of Medicine, Tokyo.

    ☆☆

    Supported in part by The Manabe Medical Foundation.

    Reprint requests: Hajime Takizawa, MD, PhD, Department of Medicine and Physical Therapy, University of Tokyo, School of Medicine, 7-3-1 Hongo, Bunkyo-ku, 113 Japan.

    ★★

    1/1/89087

    View full text