Nrf2 Knockout Attenuates the Anti-Inflammatory Effects of Phenethyl Isothiocyanate and Curcumin

被引：96

作者：

Boyanapalli, Sarandeep S. S. ^{[1
]}

Paredes-Gonzalez, Ximena ^{[1
]}

Fuentes, Francisco ^{[1
]}

Zhang, Chengyue ^{[1
]}

Guo, Yue ^{[1
]}

Pung, Doug ^{[1
]}

Saw, Constance Lay Lay ^{[1
]}

Kong, Ah-Ng Tony ^{[1
]}

机构：

[1] Rutgers State Univ, Ctr Canc Prevent Res, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2014年 / 27卷 / 12期

关键词：

NF-KAPPA-B; TRANSCRIPTION FACTOR NRF2; MOUSE PERITONEAL-MACROPHAGES; LPS-INDUCED INFLAMMATION; NITRIC-OXIDE SYNTHASE; HEME OXYGENASE-1; OXIDATIVE STRESS; GENE-EXPRESSION; ENHANCES SUSCEPTIBILITY; NATURAL PHYTOCHEMICALS;

D O I：

10.1021/tx500234h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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-alpha (TNF-alpha) 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-alpha 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.

引用

页码：2036 / 2043

页数：8

共 61 条

[1] Inflammation and cancer: How hot is the link? [J].