Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin.
Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin.
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DOI：
10.1021/tx500234h
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发表时间：
2014-12-15
影响因子：
4.1
通讯作者：
Kong AN
中科院分区：
文献类型：
--
作者：
Boyanapalli SS;Paredes-Gonzalez X;Fuentes F;Zhang C;Guo Y;Pung D;Saw CL;Kong AN
植物化学物质在预防和治疗医学中的作用是科学研究的一个主要领域。一些研究已经阐明了植物化学物质在Nrf2转录激活中的机制作用。本研究旨在通过用异硫氰酸苯乙酯(PEITC)和姜黄素(CUR)处理Nrf2+/+和Nrf2-/-小鼠的腹膜巨噬细胞来研究转录因子Nrf2的重要性。用药物对腹膜巨噬细胞进行预处理，并用脂多糖(LPS)单独或与PEITC或CUR联合攻击，根据处理细胞的基因和蛋白表达来评估它们的抗炎和抗氧化作用。定量聚合酶链式反应(QPCR)检测，LPS处理后NRF2+/+和NRF2-/-巨噬细胞中炎性标志物环氧合酶-2(COX-2)、诱导型一氧化氮合酶(INOS)、白介素6(IL-6)和肿瘤坏死因子-α(肿瘤坏死因子-α)的表达均增加。经PEITC和CUR处理的NRF2+/+巨噬细胞显示，这些抗炎基因的表达显著减少，而作为NRF2转录因子组下游的抗氧化应激基因的血红素加氧酶-1(HO-1)的表达增加。PEITC和CUR对NRF2-/-巨噬细胞的抗炎基因表达无明显影响，对HO-1表达无明显影响，但对COX-2蛋白表达有明显抑制作用，对HO-1表达有上调作用。基因敲除动物的巨噬细胞无明显变化。此外，在NRF2+/+巨噬细胞中，经PEITC处理后，内毒素诱导的IL-6和肿瘤坏死因子-α的产生显著减少，而在基因敲除动物的巨噬细胞中未见明显变化。对Nrf2+/+和Nrf2-/-小鼠的巨噬细胞进行定量聚合酶链式反应、免疫印迹和酶联免疫吸附试验的结果表明，Nrf2在PEITC和Cur的抗炎和抗氧化作用中起重要作用，而在Nrf2-/-巨噬细胞中Nrf2的活性降低。
The role of phytochemicals in preventive and therapeutic medicine is a major area of scientific research. Several studies have illustrated the mechanistic roles of phytochemicals in Nrf2 transcriptional activation. The present study aims to examine the importance of the transcription factor Nrf2 by treating peritoneal macrophages from Nrf2+/+ and Nrf2–/– mice ex vivo with phenethyl isothiocyanate (PEITC) and curcumin (CUR). The peritoneal macrophages were pretreated with the drugs and challenged with lipopolysaccharides (LPSs) alone and in combination with PEITC or CUR to assess their anti-inflammatory and antioxidative effects based on gene and protein expression in the treated cells. LPS treatment resulted in an increase in the expression of inflammatory markers such as cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in both Nrf2+/+ and Nrf2–/– macrophages, detected by quantitative polymerase chain reaction (qPCR). Nrf2+/+ macrophages treated with PEITC and CUR exhibited a significant decrease in the expression of these anti-inflammatory genes along with an increase in the expression of hemeoxygenase-1 (HO-1), which is an antioxidative stress gene downstream of the Nrf2 transcription factor battery. Although there was no significant decrease in the expression of the anti-inflammatory genes or an increase in HO-1 expression in Nrf2–/– macrophages treated with either PEITC or CUR, there was a significant decrease in the protein expression of COX-2 and an increase in the expression of HO-1 in Nrf2+/+ macrophages treated with PEITC compared to that with CUR treatment. No significant changes were observed in the macrophages from knockout animals. Additionally, there was a significant decrease in LPS-induced IL-6 and TNF-α production following PEITC treatment compared with that following CUR in Nrf2+/+ macrophages, whereas no change was observed in the macrophages from knockout animals. The results from qPCR, western blot, and ELISA analyses in macrophages from Nrf2+/+ and Nrf2 –/– mice indicate that Nrf2 plays an important role in the anti-inflammatory and antioxidative effects of PEITC and CUR, as observed by their decreased activities in Nrf2–/– macrophages.
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影响因子：
5.3
作者：
Itoh, K;Mochizuki, M;Yamamoto, M
通讯作者：
Yamamoto, M
影响因子：
8.6
作者：
Li, Ying Ji;Takizawa, Hajime;Sugawara, Isamu
通讯作者：
Sugawara, Isamu
影响因子：
9.3
作者：
Foresti, Roberta;Bains, Sandip K.;Motterlini, Roberto
通讯作者：
Motterlini, Roberto
影响因子：
5.4
作者：
Lyu, Ji Hyo;Lee, Geum San;Kim, Kyun Ha;Kim, Hyung-Woo;Cho, Su-In;Jeong, Seung-Il;Kim, Hong-Jun;Ju, Young-Seung;Kim, Ho-Kyoung;Sadikote, Ruxana T.;Christman, John W.;Oh, Sei-Ryang;Lee, Hyeong-Kyu;Ahn, Kyung-Seop;Joo, Myungsoo
通讯作者：
Joo, Myungsoo
影响因子：
5.6
作者：
Fu, Yunhe;Gao, Ruifeng;Zhang, Naisheng
通讯作者：
Zhang, Naisheng