Environmental Toxicology and Pharmacology 2013-03-01

Differential chemokine induction by 1-nitropyrene and 1-aminopyrene in bronchial epithelial cells: importance of the TACE/TGF-α/EGFR-pathway.

Johan Øvrevik, Jørn A Holme, Marit Låg, Per E Schwarze, Magne Refsnes

Index: Environ. Toxicol. Pharmacol. 35(2) , 235-9, (2013)

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Abstract

1-nitropyrene (1-NP), a common PAH in diesel exhaust, and its amine metabolite 1-aminopyrene (1-AP) induce distinctly different chemokine-responses in bronchial epithelial cells (BEAS-2B) characterized by increases in CXCL8 and CCL5, respectively. Tumor necrosis factor-α converting enzyme (TACE), which cleaves membrane-bound transforming growth factor (TGF)-α, activating the epidermal growth factor receptor (EGFR), may regulate pro-inflammatory responses induced by a variety of endogenous and exogenous agents. The present results suggest that CXCL8, but not CCL5 responses in 1-NP- or 1-AP-exposed cells required TACE/TGF-α/EGFR-signaling. The findings strengthen the notion that TACE/TGF-α/EGFR-signaling is central in epithelial CXCL8-regulation upon exposure to multiple airborne pollutants.Copyright © 2013 Elsevier B.V. All rights reserved.