Differential chemokine induction by 1-nitropyrene and 1-aminopyrene in bronchial epithelial cells: importance of the TACE/TGF-α/EGFR-pathway.
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.
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
Johan
J
Øvrevik
Jørn A
JA
Holme
Marit
M
Låg
Per E
PE
Schwarze
Magne
M
Refsnes
D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D011721:Pyrenes / Q000633:toxicity*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000378:metabolism
C508606:CXCL8 protein, human; D018925:Chemokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016209:Interleukin-8; D011721:Pyrenes; D011725:Pyridines; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C004482:1-aminopyrene; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C032668:1-nitropyrene