Mechanisms of chemokine responses by polycyclic aromatic hydrocarbons in bronchial epithelial cells: Sensitization through toll-like receptor-3 priming

作者：Ovrevik Johan^*; Refsnes Magne; Holme Jorn A; Schwarze Per E; Lag Marit

来源：Toxicology Letters, 2013, 219(2): 125-132.

DOI：10.1016/j.toxlet.2013.02.014

• Air pollution
• PAHs
• Lung cells
• Inflammation
• Cytokines

We have previously observed that 1-nitropyrene (1-NP) and its amine metabolite 1-aminopyrene (1-AP) induce differential chemokine responses in human bronchial epithelial cells (BEAS-2B) characterized by maximum responses for CXCL8 (IL-8) and CCL5 (RANTES), respectively. In the present study, we further explored the effects of 1-NP and 1-AP on chemokine responses. The results suggest that the differential effect of 1-NP and 1-AP on CXCL8 and CCL5 in BEAS-2B cells was mainly related to effects at higher concentrations, which in the case of 1-NP seemed to be linked to ROS-formation and/or metabolic activation by CYP-enzymes. However, at a low concentration (1 mu M) where neither 1-NP, 1-AP nor unsubstituted pyrene had any effect on chemokine responses, we found that all three PAHs potentiated CXCL8 and CCL5 responses induced by the TLR3 ligand polyinosinic:polycytidylic acid (Poly I:C) in BEAS-2B cells. As neither benzo[alpyrene nor beta-naphthoflavone induced a similar effect in Poly I:C-primed cells, the response seemed independent of aryl hydrocarbon receptor-mediated mechanisms. The results show that priming cells with an inflammogenic stimuli like Poly I:C sensitizes the cells toward additional proinflammatory effects of certain PAHs. The study underscores that testing on healthy cells or animals may not be sufficient to fully evaluate chemokine responses and the pro-inflammatory potential of organic chemicals.

• 出版日期2013-5-23