Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.
Environ Toxicol Pharmacol. 2013 Mar;35(2):235-9. doi: 10.1016/j.etap.2012.12.011. Epub 2013 Jan 4.
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.
1-硝基芘（1-NP）是柴油尾气中常见的多环芳烃，其胺代谢物 1-氨基芘（1-AP）分别诱导支气管上皮细胞（BEAS-2B）中截然不同的趋化因子反应，分别表现为 CXCL8 和 CCL5 的增加。肿瘤坏死因子-α转化酶（TACE）可切割膜结合的转化生长因子（TGF）-α，激活表皮生长因子受体（EGFR），可能调节多种内源性和外源性物质诱导的促炎反应。本研究结果表明，1-NP 或 1-AP 暴露细胞中 CXCL8 的产生，而不是 CCL5 的产生，需要 TACE/TGF-α/EGFR 信号通路。这些发现进一步证实了 TACE/TGF-α/EGFR 信号通路在暴露于多种空气污染物后上皮细胞 CXCL8 调节中的核心作用。
