In vitro toxicity evaluation of diesel exhaust particles on human eosinophilic cell.
Diesel exhaust particles (DEPs), comprised mainly of particles less than 2.5 microm (PM 2.5) in aerodynamic diameter, have been assumed to enhance the response of asthma to allergen inhalation. Although eosinophilic infiltration is remarkable in the event of bronchial asthma induced by DEPs, the precise mechanisms leading to eosinophilia are unknown. To examine the effect of DEPs on eosinophils, we measured the cytokine products and activity of nuclear factor-kappa B (NF-kappa B) after addition of the proteasomal inhibitor MG132 in HL-60 clone 15 cells differentiated into eosinophils. We measured eotaxin-induced chemotaxis of cells and their activity of p38 mitogen-activated protein (MAP) kinase was analysed. Interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1) were increased markedly in DEPs-treated cells. The active form of NF-kappaB in cells treated with DEPs was increased, and this effect was significantly decreased by the administration of MG132. Cell migration in the presence of DEPs was significantly greater, and inhibited by adding N-acetyl l-cysteine. P38 MAP kinase activity was highly influenced by DEPs-treatment. DEPs induce MCP-1 and IL-8 production by up-regulating NF-kappa B activity, which is inhibited in the presence of an inhibitor of proteasomal degradation. DEP also promotes eotaxin-induced chemotaxis in a p38-dependent manner.
Hirota
Ryoji
R
Department of Environmental Medicine, Kochi Medical School, Kohasu, Oko, Nakoku, Kochi 783-8505, Japan. hirotar@kochi-u.ac.jp <hirotar@kochi-u.ac.jp>
Akimaru
Kunihiro
K
Nakamura
Hiroyuki
H
D000111:Acetylcysteine / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D002999:Clone Cells; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000187:drug effects / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism
D018932:Chemokine CCL2; D016209:Interleukin-8; D007976:Leupeptins; D016328:NF-kappa B; D001335:Vehicle Emissions; D048051:p38 Mitogen-Activated Protein Kinases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine