Effects of diesel organic extracts on chemokine production by peripheral blood mononuclear cells

Background: Polyaromatic hydrocarbons (PAHs) associated with diesel exhaust particles (DEPs) are found in the atmospheric urban pollution. Such compou nds have been shown to favor IgE production, bronchial hyperresponsiveness, and airway inflammation. Chemokines are a group of chemotactic cytokines i nvolved in the recruitment of inflammatory cells. Objective: We investigated the effect of DEP-PAHs on the release and mRNA e xpression of IL-8, MCP-1, and RANTES by PBMCs obtained from healthy subject s. Methods: Protein production in supernatants was assessed by ELISA, and mRNA expression was evaluated by semiquantitative RT-PCR. Results: Secretion of IL-8 and RANTES increased in a dose-dependent manner with increasing concentrations of DEP-PAHs (range, 0.5 ng to 50 ng/mL). On the contrary, the release of MCP-1 was significantly inhibited, also in a d ose-dependent manner. Messenger RNA production coding for IL-8, RANTES, and MCP-1 showed parallel variations to the production of the correspondent pr oteins. Effects of DEP-PAHs became significant at 7 hours and up to 48 hour s time culture for MCP-1, and up to 24 hours time culture for IL-8 and RANT ES. Moreover, supernatants from DEP-PAH-activated cells, compared with thos e of controls, exhibited a significantly enhanced chemotactic activity for neutrophils and eosinophils, which was significantly inhibited by pretreatm ent with anti-IL-8 and anti-RANTES neutralizing antibodies, respectively. Conclusion: These findings suggest that the chemokine pathways are modulate d by DEP-PAHs at the transcriptional level, reinforcing the idea that the d evelopment of inflammatory reactions might be affected by diesel exhaust em ission.