Synergistic effect of diesel organic extracts and allergen Der p 1 on the release of chemokines by peripheral blood mononuclear cells from allergic subjects - Involvement of the MAP kinase pathway

The organic compounds of diesel exhaust particles (DEP-PAHs) have been show n to favor immunoglobulin production and bronchial hyperresponsiveness and to affect cytokine and chemokine productions. To evaluate if diesel exhaust could act in synergy with a house dust mite allergen (Der p 1), peripheral blood mononuclear cells from allergic patients were exposed to DEP-PAHs, w ith or without purified Der p 1. DEP-PAHs and Der p 1 separately induced an increase in interleukin (IL)-8, regulated on activation, normal T cells ex pressed and secreted (RANTES), and tumor necrosis factor-alpha concentratio ns. Interestingly, a synergy between the two stimuli was also observed. In the Ease of monocyte chemotactic protein (MCP)-1, DEP-PAHs reduced the rele ase, whereas Der p 1 enhanced it. A simultaneous exposure led to reduced pr oduction as compared with allergen exposure alone, but still represented an increase as compared with the control exposure. Mitogen-activated protein (MAP) kinase Erk1/2 antagonist mainly inhibited the release of MCP-1, where as MAP kinase p38 antagonist mainly suppressed the release of IL-8 and RANT ES. Messenger RNA expression correlated with protein measurements. Moreover , supernatants from cells exposed to both DEP-PAHs and Der p 1 had a signif icant chemotactic activity on neutrophils and eosinophils, These findings s uggest that simultaneous exposure of allergic patients to DEPs and allergen s could result in high local chemokine levels via MAP kinase pathways activ ation, increasing the likelihood of reaching a critical threshold leading t o the initiation of respiratory allergic symptoms.