Cigarette smoke extract (CSE) induces transient receptor potential ankyrin 1(TRPA1) expression via activation of HIFI cdn A549 cells
Cigarette smoke extract (CSE) induces transient receptor potential ankyrin 1(TRPA1) expression via activation of HIFI cdn A549 cells
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香烟烟雾提取物 (CSE) 通过激活 A549 细胞中的 HIF1alpha 诱导瞬时受体电位锚蛋白 1 (TRPA1) 表达。
DOI：
10.1016/j.freeradbiomed.2016.07.028
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发表时间：
2016-10-01
影响因子：
7.4
通讯作者：
Zhong, Nanshan
中科院分区：
文献类型：
--
作者：
Nie, Yichu;Huang, Chuqin;Zhong, Nanshan
我们以前发现，瞬时受体电位锚蛋白1（TRPA 1）在豚鼠气管上皮细胞的香烟烟雾（CS）暴露14天后升高。然而，CS诱导TRPA 1表达的机制仍然未知。在这里，我们探讨了香烟烟雾提取物（CSE）诱导的TRPA 1表达是否与A549细胞中HIF 1 α的调节有关。我们的研究结果表明，CSE增加了A549细胞中TRPA 1的表达，降低了I κ B、PHD 2和HDAC 2，增加了ROS释放和NF-κ B和HIF 1 α的核转位。此外，HIF 1 α siRNA和/或MG 132（蛋白酶体抑制剂）预处理显著抑制CSE诱导的TRPA 1表达和A549细胞中的HIF 1 α核转位。然而，HIFloc siRNA预处理不影响CSE诱导的NF-κ B核转位，表明CSE诱导的A549细胞中TRPA 1表达由HIFloc直接介导，而不是由NF-κ B介导。与CSE处理相似，用LPS处理A549细胞引起NF-κ B核转位和HIFloc mRNA表达的显著增加，但不改变TRPA 1 mRNA表达。然而，用PHD 2 siRNA预处理确实导致LPS处理的A549细胞中TRPA 1 mRNA表达增加;这种作用被SN 50（NF-κ B抑制剂）抑制。提示NF-κ B通过调节HIFloc mRNA转录间接调节TRPA 1 mRNA表达。另外，HDAC 2 siRNA联合2%CSE处理细胞后，HIFI α核转位和TRPA 1表达增加，而MG 132和HIFI α siRNA可显著抑制HIFI α核转位和TRPA 1表达。这些结果表明，HDAC 2通过促进HIFloc的DNA结合活性间接调节TRPA 1的表达。这些发现表明，CSE通过直接激活HIFloc增加气道上皮细胞中的TRPA 1表达，并且TRPA 1表达的这种增加通过NF-κ B、PHD 2和HDAC 2调节HIFloc活性而间接调节。(C)2016由Elsevier Inc.出版
We previously found that transient receptor potential ankyrin 1 (TRPA1) in guinea pig tracheal epithelial cells was elevated after 14 days of cigarette smoke (CS) exposure. However, the mechanism underlying CS-induced TRPA1 expression remains unknown. Here, we explored whether cigarette smoke extract (CSE)-induced TRPA1 expression is related with modulation of HIF1 alpha in A549 cells. Our results showed that CSE increased TRPA1 expression in A549 cells, decreased I kappa B, PHD2, and HDAC2, and increased ROS release and nuclear translocation of NF-kappa B and HIF1 alpha. Moreover, HIF1 alpha siRNA and/or MG132 (a proteasome inhibitor) pretreatment significantly inhibited CSE-induced TRPA1 expression and HIF1 alpha nuclear translocation in A549 cells. However, HIFloc siRNA pretreatment did not affect CSE-induced NF-kappa B nuclear translocation, suggesting that CSE-induced TRPA1 expression in A549 cells is directly mediated by HIFloc, but not by NF-kappa B. Similar to CSE treatment, treatment of A549 cells with LPS caused significant increases in nuclear translocation of NF-kappa B and HIFloc mRNA expression, but did not alter TRPA1 mRNA expression. However, pretreatment with PHD2 siRNA did result in increased TRPA1 mRNA expression in LPS-treated A549 cells; an effect that was inhibited by SN50 (a NF-kappa B inhibitor). It suggests a role for NF-kappa B to indirectly regulate TRPA1 mRNA expression via modulating HIFloc mRNA transcription. In addition, treatment cells with HDAC2 siRNA plus 2%CSE resulted in increased HIFI oc nuclear trans location and TRPA1 expression, which was significantly inhibited by MG132 and HIFI oc siRNA. These results suggest that HDAC2 indirectly modulates TRPA1 expression by promoting the DNA-binding activity of HIFloc. These findings show that CSE increases TRPA1 expression in airway epithelial cells by directly activating HIFloc, and that this increase in TRPA1 expression is indirectly regulated via NF-kappa B, PHD2 and HDAC2 modulation of HIFI oc activity. (C) 2016 Published by Elsevier Inc.