Advertisement

Inflammation

, Volume 41, Issue 3, pp 784–794 | Cite as

Effect of Atmospheric PM2.5 on Expression Levels of NF-κB Genes and Inflammatory Cytokines Regulated by NF-κB in Human Macrophage

  • Yuezhu Zhang
  • Shuyue Wang
  • Jian Zhu
  • Chunyan Li
  • Tianrong Zhang
  • Hongbo Liu
  • Qi Xu
  • Xiaofang Ye
  • Liting Zhou
  • Lin Ye
ORIGINAL ARTICLE

Abstract

Exposure to PM2.5 induces systemic inflammation, and the NF-κB signaling pathway plays an important role in the inflammation process. We aim to clarify whether the expression of NF-κB gene family affects inflammation caused by PM2.5. Human monocytic cells (THP-1) were induced to differentiate into macrophages using phorbol myristate acetate. The macrophages were then treated with 100, 200, and 400 μg/ml of PM2.5 for 12, 24, and 48 h, respectively. Then, we determined the survival rate of macrophages through the MTT assay. The TNF-α and CRP levels in the cell culture medium were measured through enzyme-linked immunosorbent assay. The NF-κB1, NF-κB2, RelA, RelB, and Rel mRNA levels in macrophages were measured with reverse transcriptase-polymerase chain reaction. As a consequence, the survival rate of macrophages decreased with increasing PM2.5 exposure time and dose. The TNF-α levels in PM2.5-treated groups were lower as compared with the control group and in contrast to the NF-κB mRNA levels at all exposure times. The TNF-α level in the 400-μg/ml group and the NF-κB1, NF-κB2, RelB, and Rel mRNA levels in all PM2.5-treated groups were found to be higher at 24 h than at 12 h. Furthermore, the TNF-α, CRP, and NF-κB2 mRNA levels in the group treated with 400 μg/ml PM2.5 were higher at 48 h that at 12 and 24 h. On the other hand, the NF-κB1, RelA, RelB, and Rel mRNA levels in all PM2.5-treated groups were lower as compared to levels of TNF-α, CRP, and NF-κB2 mRNA. The levels of NF-κB genes and inflammatory cytokines demonstrated different correlations at different exposure times. Therefore, we conclude that PM2.5 reduces the survival rate of macrophages. As macrophages are exposed to PM2.5, the NF-κB gene family expression is increased, which subsequently affects inflammatory factor levels.

KEY WORDS

PM2.5 cytotoxicity NF-κB inflammatory cytokines 

Notes

Acknowledgements

This work was sponsored by the Natural Science Foundation of Department of Science and Technology of Jilin Province (20150101208JC), Medical Research Support Plan of Norman Bethune Health Science Center (2013102010), and Shanghai Key Laboratory of Meteorology and Health (QXJK201506). We would like to acknowledge the Animal Resources Centre for animal technical support.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Gualtieri, M., P. Mantecca, V. Corvaja, et al. 2009. Winter fine particulate matter from Milan induces morphological and functional alterations in human pulmonary epithelial cells (A549). Toxicology Letters 188: 52–62.CrossRefPubMedGoogle Scholar
  2. 2.
    Zhao, Jinzhuo, Liang Bo, Changyi Gong, et al. 2015. Preliminary study to explore gene-PM2.5 interactive effects on respiratory system in traffic policemen. International Journal of Occupational Medicine and Environmental Health 28 (6): 971–983.CrossRefPubMedGoogle Scholar
  3. 3.
    Gan, W.Q., J.M. Fitz Gerald, C. Carlsten, et al. 2013. Association ambient air pollution with chronic obstructive pulmonary disease hospitalization and mortality. American Journal of Respiratory and Critical Care Medicine 187 (7): 721–727.CrossRefPubMedGoogle Scholar
  4. 4.
    Carere, A., A. Stammati, F. Zucco, et al. 2002. In vitro toxicology methods: impact on regulation from technical and scientific advancements. Toxicology Letters 127: 153–160.CrossRefPubMedGoogle Scholar
  5. 5.
    Oberdörster, G., E. Oberdörster, and J. Oberdörster. 2005. Nanotoxocology: an emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives 113: 823–839.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ferguson, Matthew D., et al. 2013. Comparison of how ambient PMc and PM2.5 influence the inflammatory potential. Inhalation Toxicology 25 (14): 766–773.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Meng, Ziqiang, and Quanxi Zhang. 2007. Damage effects of dust storm PM2.5 on DNA in alveolar macrophages and lung cells of rats. Food and Chemical Toxicology 45: 1368–1374.CrossRefPubMedGoogle Scholar
  8. 8.
    Shukla, A., C. Timbfin, K. BeruBe, et al. 2000. Inhaled particulate matter causes expression of nuclear factor (NF)-κB-related genes and oxidant-dependent NF-κB activation in vitro. American Journal of Respiratory Cell and Molecular Biology 1 (23): 182–187.CrossRefGoogle Scholar
  9. 9.
    Baker, Rebecca G., Matthew S. Hayden, and Sankar Ghosh. 2010. NF-κB, inflammation and metabolic disease. Cell Metabolism 12 (8): 11–22.Google Scholar
  10. 10.
    Craig, R., A. Larkin, A.M. Mingo, et al. 2000. p38 MARK and NF-kappa B collaborate to induce interleukin-6 gene expression and release. The Journal of Biological Chemistry 275 (31): 23814–23824.CrossRefPubMedGoogle Scholar
  11. 11.
    Tominaga, K., K. Higuchi, M. Tsuno, et al. 2000. Induction of signal transduction pathways in rat gastric epithelial cells stimulated with interleukin-1beta. Alimentary Pharmacology & Therapeutics 14 (Suppl): 1101–1108.Google Scholar
  12. 12.
    Takeda, K., T. Kaisho, and S. Akira. 2003. Toll-like receptors. An2nu Revue d'Immunologie 21: 335–376.CrossRefGoogle Scholar
  13. 13.
    Srivastava, Satish K., and Kota V. Ramana. 2009. Focus on molecules: nuclear factor-kappa B. Experimental Eye Research 88: 2–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Nam, Hae Yun, Byung Hyune Choi, Joo Yong Lee, et al. 2004. The role of nitric oxide in the particular matter (PM2.5)-induced NF-κB activation in lung epithelial cells. Toxicology Letters 148: 95–102.CrossRefPubMedGoogle Scholar
  15. 15.
    Dagher, Z., G. Garcon, and S. Billet. 2007. Role of nuclear factor-kappa B activation in adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture. Appl Toxicology 27 (3): 284–290.CrossRefGoogle Scholar
  16. 16.
    Schikowski, T., D. Sugiri, U. Ranft, et al. 2005. Long-term air pollution exposure and living close to busy roads are associated with COPD in women. Pespir Res 6: 152–176.CrossRefGoogle Scholar
  17. 17.
    Yadav, A., K. Kumar, A. Kasim, et al. 1998. Visibility and incidence of respiratory disease during the haze episode in Brunei Darussalam. Pure and Applied Geophysics 160 (1–2): 265.Google Scholar
  18. 18.
    Lonati, G., M. Giugliano, and S. 2008. Ozgen, primary and secondary components of PM2.5 in Milan (Italy). Environment International 34: 665–670.CrossRefPubMedGoogle Scholar
  19. 19.
    Chen, L.C., and M. Lippmann. 2009. Effects of metals within ambient air particulate matter (PM) on human health. Inhalation Toxicology 21: 1–31.CrossRefPubMedGoogle Scholar
  20. 20.
    Shang, Y., T. Zhu, A.G. Lenz, et al. 2013. Reduced in vitro toxicity of fine particulate matter collected during the 2008 Summer Olympic Games in Beijing: the roles of chemical and biological components. Toxicology In Vitro 27: 2084–2093.CrossRefPubMedGoogle Scholar
  21. 21.
    Pavagadhi, S., R. Betha, S. Venkatesan, et al. 2013. Physicochemical and toxicological characteristics of urban aerosols during a recent Indonesian biomass burning episode. Environmental Science and Pollution Research International 20: 2569–2578.CrossRefPubMedGoogle Scholar
  22. 22.
    Cavanagh, J.A., K. Trought, L. Brown, and S. Duggan. 2009. Exploratory investigation of the chemical characteristics and relative toxicity of ambient air particulates from two New Zealand cities. Sci Total Environ 407: 5007–5018.CrossRefPubMedGoogle Scholar
  23. 23.
    Steenhof, M., I. Gowns, M. Strak, et al. 2011. In vitro toxicity of particulate matter (PM) collected at different sites in the Netherlands is associated with PM composition, size fraction and oxidative potential—the RAPTES project. Particle and Fibre Toxicology 8: 26–32.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Haddad, J.J. 2004. Redox and oxidant-mediated regulation of apoptosis signaling pathways: immuno-pharmaco-redox conception of oxidative siege versus cell death commitment. Immunopharma-cology 4: 475–493.Google Scholar
  25. 25.
    Mason, N. 2002. Cutting edge: identification of c-Rel-dependent and -independent pathways of IL-12 production during infectious and inflammatory stimuli. Immunol 168: 2590–2594.CrossRefGoogle Scholar
  26. 26.
    Caamano, J., et al. 1999. The NF-KB family member Re1B is required for innate and adaptive immunity to Toxoplasma gondii. Immunol 163: 4453–4461.Google Scholar
  27. 27.
    Billet, S., G. Garcon, Z. Dagher, et al. 2007. Ambient particulate matter (PM2.5): physicochemical characterization and metabolic activation of the organic fraction in human lung epithelial cells (A549). Environmental Research 105: 212–223.CrossRefPubMedGoogle Scholar
  28. 28.
    Rumelhard, M., K. Ramgolam, F. Auger, A. Baeza-Squiban, et al. 2007. Effects of PM2.5 components in the release of amphiregulin by human airway epithelial cells. Toxicology Letters 168: 155–164.CrossRefPubMedGoogle Scholar
  29. 29.
    Lepers, C., V. Andre, M. Dergham, et al. 2014. Xenobiotic metabolism induction and bulky DNA adducts generated by particulate matter pollution in BEAS-2B cell line: geographical and seasonal influence. Journal of Applied Toxicology 34: 703–713.CrossRefPubMedGoogle Scholar
  30. 30.
    Dergham, M., C. Lepers, A. Verdin, et al. 2012. Prooxidant and proinflammatory potency of air pollution particulate matter (PM) produced in rural, urban, or industrial surroundings in human bronchial epithelial cells (BEAS-2B). Chemical Research in Toxicology 25: 904–919.CrossRefPubMedGoogle Scholar
  31. 31.
    Tablin, F., L.J. den Hartigh, H.H. Aung, et al. 2012. Seasonal influences on CAPS exposures: differential responses in platelet activation, serum cytokines and xenobiotic gene expression. Inhalation Toxicology 24 (8): 506–517.CrossRefPubMedGoogle Scholar
  32. 32.
    Nurkiewicz TR, Porter DW, Hubbs AF, et al. 2011. Pulmonary particulate matter and systemic microvascular dysfunction. Research Report/Health Effects Institute 164: 3-48-60.Google Scholar
  33. 33.
    Takabayashi, K., M. Corr, T. Hayashi, V. Redecke, et al. 2006. Effects of subchronic exposures to macrophage and negative regulator of gene expression. Immunity 24: 475–487.CrossRefGoogle Scholar
  34. 34.
    Welsch, T., S.A. Müller, A. Ulrich, A. Kischlat, U. Hinz, P. Kienle, M.W. Büchler, J. Schmidt, and B.M. Schmied. 2007. C-reactive protein as early predictor for infectious postoperative complications in rectal surgery. International Journal of Colorectal Disease 22 (12): 1499–1507.CrossRefPubMedGoogle Scholar
  35. 35.
    Pinto-Plata, V.M., H. Mullerova, J.F. Toso, et al. 2006. C-restive protein in patients with COPD, control smokers and non-smokers. Thorax 61 (4): 23–28.PubMedGoogle Scholar
  36. 36.
    Wang, Hetong, Laiyu Song, Ju Wenhui, et al. 2017. The acute airway inflammation induced by PM2.5 exposure and the treatment of essential oils in Balb/c mice. Scientific Reports 7: 44256.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Jalava, P.L., M.R. Hirvonen, M. Sillanpaa, et al. 2009. Associations of urban air particulate composition with inflammatory and cytotoxic responses in RAW 246.7 cell line. Inhalation Toxicology 21: 994–1006.CrossRefPubMedGoogle Scholar
  38. 38.
    Pozzi, R., B. De Berardis, L. Paoletti, et al. 2003. Inflammatory mediators induced by coarse (PM2.5-10) and fine (PM2.5) urban air particles in RAW 264.7 cells. Toxicology 183: 243–254.CrossRefPubMedGoogle Scholar
  39. 39.
    Williams, R.O., E. Paleolog, and M. Feldmann. 2007. Cytokine inhibitors in rheumatoid arthritis and other autoimmune diseases. Current Opinion in Pharmacology 7 (4): 412–417.CrossRefPubMedGoogle Scholar
  40. 40.
    Lee, I.T., and C.M. Yang. 2013. Inflammatory signalings involved in airway and pulmonary diseases. Mediators of Inflammation 2013 (791231).Google Scholar
  41. 41.
    Maciejczyk, P., and L.C. Chen. 2005. Effects of subchronic exposures to concentrated ambient particles (CAPS) in mice. VIII. Source-related daily variations in in vitro responses to CAPS. Inhalation Toxicology 17: 243–253.CrossRefPubMedGoogle Scholar
  42. 42.
    Bourgeois, B., and J.W. Owens. 2014. The influence of Hurricanes Katrina and Rita on the inflammatory cytokine response and protein expression in A549 cells exposed to PM2.5 collected in the Baton Rouge-Port Allen industrial corridor of Southeastern Louisiana in 2005. Toxicology Mechanisms and Methods 24: 220–242.CrossRefPubMedGoogle Scholar
  43. 43.
    Winsauer, G., and R. Martin. 2007. Resolution of inflammation: intracellular feedback loops in the endothelium. Thrombosis and Haemostasis 97: 364–369.CrossRefPubMedGoogle Scholar
  44. 44.
    Yamazaki, S., T. Muta, and K. Takeshige. 2001. A novel IKB protein, IKB-zeta, induced by proinflammatory stimuli, negatively regulates nuclear factor-KB in the nuclei. Journal of Biological Chemistry 276 (29): 27667–27662.Google Scholar
  45. 45.
    Medzhitov, R. 2008. Origin physiological roles of inflammation. Nature 454: 428–435.CrossRefPubMedGoogle Scholar
  46. 46.
    Serhan, C.N., and J. Savill. 2005. Resolution of inflammation: the beginning programs the end. Nature Immunology 6: 1191–1197.CrossRefPubMedGoogle Scholar
  47. 47.
    Haddad, J.J. 2004. Redox and oxidant-mediated regulation of apoptosis signaling pathways: immuno-pharmaco-redox conception of oxidative siege versus cell death commitment. International Immunopharmacology 4: 475–493.CrossRefPubMedGoogle Scholar
  48. 48.
    Grigoriadis, G. 1996. The Rel subunit of NF-κB- like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for Rel in different macrophage populations. EMBO 15: 7099–7107.CrossRefGoogle Scholar
  49. 49.
    Baulig, A., S. Singly, A. Marchand, R. Schins, et al. 2009. Role of Paris PM2.5 components in the pro-inflammatory response induced in airway epithelial cells. Toxicology 261: 126–135.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yuezhu Zhang
    • 1
  • Shuyue Wang
    • 2
  • Jian Zhu
    • 1
  • Chunyan Li
    • 1
  • Tianrong Zhang
    • 1
  • Hongbo Liu
    • 1
  • Qi Xu
    • 1
  • Xiaofang Ye
    • 3
  • Liting Zhou
    • 1
    • 4
  • Lin Ye
    • 1
    • 4
  1. 1.Department of Occupational and Environmental Health, School of Public HealthJilin UniversityChangchunChina
  2. 2.Department of Emergency, China-Japan Union HospitalJilin UniversityChangchunChina
  3. 3.Shanghai Key Laboratory of Meteorology and HealthShanghaiChina
  4. 4.ChangchunChina

Personalised recommendations