Mechanisms involved in pro-inflammatory responses to traffic-derived particulate matter (PM) in THP-1 macrophages compared to HBEC3-KT bronchial epithelial cells.

Journal: Toxicology
Published Date: May 7, 2025

Abstract

The pro-inflammatory responses in THP-1-derived macrophages and human bronchial epithelial cells (HBEC3-KT) were examined after exposure to size-fractioned particulate matter (PM) sampled in two road tunnels. All tunnel PM samples induced release and expression of CXCL8 and IL-1β in THP-1 macrophages (50µg/mL) and HBEC3-KT cells (100µg/mL), but the potency of the samples differed between the cell types. The road tunnel PM induced pro-inflammatory responses in the macrophages to a much higher extent than diesel exhaust particles (DEP) and particles derived from the stone materials used in the asphalt. Tunnel PM induced a markedly higher increase in cytochrome P450 (CYP)1A1 expression in HBEC3-KT cells than in THP-1 macrophages. The content of organic carbon (OC) in PM correlated to the release of CXCL8 in HBEC3-KT cells, but not in THP-1 macrophages. Moreover, the aryl hydrocarbon receptor (AhR)-inhibitor CH223191 and the antioxidant N-acetyl cysteine (NAC) reduced the PM-induced cytokine release in the macrophages to a lower extent than in HBEC3-KT. In contrast, a toll-like receptor (TLR)2 antibody markedly reduced the PM-induced responses in THP-1 macrophages, but not in HBEC3-KT. A TLR4 antibody was without effect in both cell types. The levels of the microbial TLR2-ligand β-glucan in the PM samples were in a range that might be sufficient to induce pro-inflammatory responses. However, a microbial-independent mechanism could also be involved. In support of such a mechanism, the pro-inflammatory responses to a sample of α-quartz (Min-U-Sil 5), with low levels of β-glucan, were reduced by anti-TLR2. In conclusion, our results indicate that traffic-derived PM exert pro-inflammatory responses in THP-1 macrophages and HBEC3-KT cells via different PM constituents and mechanisms. OC/AhR-dependent mechanisms appeared to be important for PM-induced CXCL8 responses in HBEC3-KT cells, while the cytokine responses in THP-1 macrophages seemed to involve TLR2-mediated activation, either via β-glucan-dependent or -independent mechanisms.

Authors

  • Marit Låg
    Department of Air quality and Noise, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: marit.lag@fhi.no.
  • Tonje Skuland
    Department of Air quality and Noise, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Jarle Ballangby
    Department of Air quality and Noise, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Vegard Sæter Grytting
    Department of Air quality and Noise, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Rikke Bramming Jørgensen
    Department of Industrial Economics and Technology Management, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
  • Brynhild Snilsberg
    Norwegian Public Roads Administration, Trondheim, Norway.
  • Johan Øvrevik
    Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Jørn A Holme
    Department of Air quality and Noise, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Magne Refsnes
    Department of Air quality and Noise, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.

Keywords

No keywords available for this article.

External Resources

Popular Topics
Recent Journals