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

Am J Respir Cell Mol Biol. 2000 Aug;23(2):247-54. doi: 10.1165/ajrcmb.23.2.4116.


The organic compounds of diesel exhaust particles (DEP-PAHs) have been shown 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, with 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 expressed and secreted (RANTES), and tumor necrosis factor-alpha concentrations. Interestingly, a synergy between the two stimuli was also observed. In the case of monocyte chemotactic protein (MCP)-1, DEP-PAHs reduced the release, whereas Der p 1 enhanced it. A simultaneous exposure led to reduced production 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, whereas MAP kinase p38 antagonist mainly suppressed the release of IL-8 and RANTES. Messenger RNA expression correlated with protein measurements. Moreover, supernatants from cells exposed to both DEP-PAHs and Der p 1 had a significant chemotactic activity on neutrophils and eosinophils. These findings suggest that simultaneous exposure of allergic patients to DEPs and allergens could result in high local chemokine levels via MAP kinase pathways activation, increasing the likelihood of reaching a critical threshold leading to the initiation of respiratory allergic symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Dermatophagoides
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Chemotaxis
  • Child, Preschool
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Glutathione / pharmacology
  • Glycoproteins / adverse effects*
  • Humans
  • Hypersensitivity / etiology
  • Hypersensitivity / metabolism*
  • Imidazoles / pharmacology
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • MAP Kinase Signaling System / drug effects
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Pyridines / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Vehicle Emissions / adverse effects*


  • Antigens, Dermatophagoides
  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokines
  • Culture Media, Conditioned
  • Cytokines
  • Enzyme Inhibitors
  • Flavonoids
  • Glycoproteins
  • Imidazoles
  • Interleukin-8
  • Pyridines
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Vehicle Emissions
  • Mitogen-Activated Protein Kinases
  • Glutathione
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one