6 research outputs found
Nrf2 Knockout Attenuates the Anti-Inflammatory Effects of Phenethyl Isothiocyanate and Curcumin
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<sup>+/+</sup> and Nrf2<sup>–/–</sup> mice <i>ex vivo</i> 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<sup>+/+</sup> and Nrf2<sup>–/–</sup> macrophages, detected by quantitative
polymerase chain reaction (qPCR). Nrf2<sup>+/+</sup> 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<sup>–/–</sup> 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<sup>+/+</sup> 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<sup>+/+</sup> 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<sup>+/+</sup> and Nrf2 <sup>–/–</sup> 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<sup>–/–</sup> macrophages