ERK-dependent induction of TNF alpha expression by the environmental contaminant benzo(a)pyrene in primary human macrophages

作者：Lecureur V^*; Le Ferrec E; N'diaye M; Le Vee M; Gardyn C; Gilot D; Fardel O

来源：FEBS LETTERS, 2005, 579(9): 1904-1910.

DOI：10.1016/j.febslet.2005.01.081

• benzo(a)pyrene
• extracellular signal-regulated protein kinase
• macrophages
• polycyclic aromatic hydrocarbon
• receptor Ah
• TNF alpha

Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are toxic environmental contaminants known to enhance production of pro-inflammatory cytokines such as IL-1 beta. The present study was designed in order to determine whether TNF alpha, another cytokine acting in inflammation, may also constitute a target for these chemicals. Both TNF alpha mRNA and TNF alpha secretion levels were found to be enhanced in human BP-treated macrophages. Dioxin, a contaminant activating the aryl hydrocarbon receptor (AhR) like PAHs, was also shown to increase TNF alpha expression. BP-mediated TNF alpha induction was however not suppressed by AhR antagonists, making unlikely the involvement of the typical AhR signalling pathway. BP-exposure of macrophages did not enhance NF-kappa B DNA binding activity, but it activated the MAP kinase ERK1/2. In addition, the use of chemical inhibitors of extracellular signal-regulated protein kinase (ERK) activation fully abrogated induction of TNFa production in BP-treated macrophages. These data likely indicate that PAHs enhance TNF alpha expression in human macrophages through an ERK-related mechanism. Such a regulation may contribute to confer pro-inflammatory properties to these widely-distributed environmental contaminants.

• 出版日期2005-3-28