Inhibitory effect of particulate matter on toll-like receptor 9 stimulated dendritic cells by downregulating mitogen-activated protein kinase and NF-κB pathway

ABSTRACT

Ambient particulate matter (PM) is associated with adverse health consequences. However, the influence of PM on the innate immune system is poorly understood. The aim of the present study was to examine the effect of diesel particulate matter 2.5 μm (PM_2.5, SRM1650b) on dendritic cells. PM_2.5 significantly reduced cytokine levels of interleukin (IL)-12 p40, IL-6 and TNF-α levels in CpG-DNA (TLR9 ligand)-stimulated dendritic cells. To determine the mechanisms underlying this observed inhibition induced by PM_2.5, western blot analysis was conducted. PM_2.5 was found to downregulate ERK1/2, JNK1/2, p38 MAPKs, and NF-κB pathways. PM_2.5 exposure decreased TLR9-dependent NF-κB and activator protein (AP-1) reporter luciferase activities. Our findings demonstrate that PM_2.5 reduced the production of cytokines which may be associated with inhibition of MAPK and NF-κB signaling pathway. Further, data suggest the immunosuppressive effect of PM_2.5 on the innate immune cells may lead to serious damage to the host immune system.

KEYWORDS:

• Diesel particulate matter
• inhibitory effect
• TLR
• MAPK
• NF-κB

Acknowledgments

This investigation was supported by the 2020 Scientific Promotion Program funded by Jeju National University, and grants from the Basic Research Laboratory Program (NRF-2017R1A4A1014512) by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (MSIP) of the Korean government, and by the Basic Research Program through the National Research Foundation of Korea (NRF) funded by Ministry of Education (NRF-2015R1D1A1A01059218).

Author contributions

M.A., I.A., and Y.-S.K. conceived and designed the experiments and wrote the paper; M.A. and I.A. performed the experiments; M.A., I.A., and Y.-S.K. analyzed the data; H.-K.K. and J.-W.H. contributed reagents/materials/analysis tools.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the 2020 Scientific Promotion Program funded by Jeju National University, and grants from the Basic Research Laboratory Program [NRF-2017R1A4A1014512] by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (MSIP) of the Korean government, and by the Basic Research Program through the National Research Foundation of Korea (NRF) funded by Ministry of Education [NRF-2015R1D1A1A01059218].