Differential effects of nitro-PAHs and amino-PAHs on cytokine and chemokine responses in human bronchial epithelial BEAS-2B cells

Journal Article · Mon Feb 01 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.10.017· OSTI ID:21344849

Ovrevik, J ^[1]; Arlt, V M ^[2]; Oya, E ^[1]; Nagy, E ^[2]; Mollerup, S ^[3]; Phillips, D H ^[2]; Lag, M; Holme, J A ^[1]

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1. Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway)
2. Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey SM2 5NG (United Kingdom)
3. Section for Toxicology, National Institute of Occupational Health, N-0033 Oslo (Norway)

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.

• OSTI ID: 21344849
• Journal Information: Toxicology and Applied Pharmacology, Vol. 242, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.10.017; PII: S0041-008X(09)00455-4; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AIR POLLUTION
APOPTOSIS
CARCINOGENS
CONDENSED AROMATICS
DNA DAMAGES
GENES
INFLAMMATION
LUNGS
LYMPHOKINES
MEN
POLYCYCLIC AROMATIC HYDROCARBONS
TOXICITY
ANIMALS
AROMATICS
BODY
GROWTH FACTORS
HYDROCARBONS
MALES
MAMMALS
MAN
MITOGENS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
POLLUTION
PRIMATES
PROTEINS
RESPIRATORY SYSTEM
SYMPTOMS
VERTEBRATES