title: Differential effects of nitro-PAHs and amino-PAHs on cytokine and chemokine responses in human bronchial epithelial BEAS-2B cells.
abstract: Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are found in diesel exhaust and air pollution particles. Along with other PAHs, many nitro-PAHs possess mutagenic and carcinogenic properties, but their effects on pro-inflammatory processes and cell death are less known. In the present study we examined the effects of 1-nitropyrene (1-NP), 3-nitrofluoranthene (3-NF) and 3-nitrobenzanthrone (3-NBA) and their corresponding amino forms, 1-AP, 3-AF and 3-ABA, in human bronchial epithelial BEAS-2B cells. The effects of the different nitro- and amino-PAHs were compared to the well-characterized PAH benzo[a]pyrene (B[a]P). Expression of 17 cytokine and chemokine genes, measured by real-time PCR, showed that 1-NP and 3-NF induced a completely different cytokine/chemokine gene expression pattern to that of their amino analogues. 1-NP/3-NF-induced responses were dominated by maximum effects on CXCL8 (IL-8) and TNF-alpha expression, while 1-AP-/3-AF-induced responses were dominated by CCL5 (RANTES) and CXCL10 (IP-10) expression. 3-NBA and 3-ABA induced only marginal cytokine/chemokine responses. However, 3-NBA exposure induced considerable DNA damage resulting in accumulation of cells in S-phase and a marked increase in apoptosis. B[a]P was the only compound to induce expression of aryl hydrocarbon receptor (AhR)-regulated genes, such as CYP1A1 and CYP1B1, but did not induce cytokine/chemokine responses in BEAS-2B cells. Importantly, nitro-PAHs and amino-PAHs induced both qualitatively and quantitatively different effects on cytokine/chemokine expression, DNA damage, cell cycle alterations and cytotoxicity. The cytokine/chemokine responses appeared to be triggered, at least partly, through mechanisms separate from the other examined endpoints. These results confirm and extend previous studies indicating that certain nitro-PAHs have a considerable pro-inflammatory potential.
authors.affiliation: Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway. johan.ovrevik@fhi.no
authors.forename: J
authors.initials: J
authors.lastname: Ovrevik
authors.forename: V M
authors.initials: VM
authors.lastname: Arlt
authors.forename: E
authors.initials: E
authors.lastname: Oya
authors.forename: E
authors.initials: E
authors.lastname: Nagy
authors.forename: S
authors.initials: S
authors.lastname: Mollerup
authors.forename: D H
authors.initials: DH
authors.lastname: Phillips
authors.forename: M
authors.initials: M
authors.lastname: Låg
authors.forename: J A
authors.initials: JA
authors.lastname: Holme
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000187:drug effects* / Q000235:genetics; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000633:toxicity*; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D000393:Air Pollutants; D018925:Chemokines; D016207:Cytokines; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene