title: Mechanisms of chemokine responses by polycyclic aromatic hydrocarbons in bronchial epithelial cells: sensitization through toll-like receptor-3 priming.
abstract: 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 μM) 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[a]pyrene nor β-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 pro-inflammatory 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.
authors: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway. johan.ovrevik@fhi.no
authors: Johan
authors: J
authors: Øvrevik
authors: Magne
authors: M
authors: Refsnes
authors: Jørn A
authors: JA
authors: Holme
authors: Per E
authors: PE
authors: Schwarze
authors: Marit
authors: M
authors: Låg
mesh_terms: D015153:Blotting, Western; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D011070:Poly I-C / Q000494:pharmacology; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011721:Pyrenes / Q000633:toxicity; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species; D051196:Toll-Like Receptor 3 / Q000187:drug effects*
chemical_list: D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051196:Toll-Like Receptor 3; D003577:Cytochrome P-450 Enzyme System; C004482:1-aminopyrene; D011070:Poly I-C; C032668:1-nitropyrene