- Author:
Yu-fan SHEN
1
;
Xue ZHANG
2
;
Ying WANG
2
;
Fan-fan CAO
2
;
Georges UZAN
2
;
Bin PENG
2
;
Deng-hai ZHANG
2
Author Information
- Publication Type:Journal Article
- MeSH: Hep G2 Cells; Humans; Interleukin-1 Receptor-Associated Kinases; antagonists & inhibitors; NF-kappa B; antagonists & inhibitors; metabolism; Phosphorylation; Toll-Like Receptor 4; antagonists & inhibitors; physiology; Triterpenes; pharmacology
- From: Journal of Integrative Medicine 2016;14(3):203-208
- CountryChina
- Language:English
-
Abstract:
OBJECTIVECelastrol has been established as a nuclear factor-κB (NF-κB) activation inhibitor; however, the exact mechanism behind this action is still unknown. Using text-mining technology, the authors predicted that interleukin-1 receptor-associated kinases (IRAKs) are potential celastrol targets, and hypothesized that targeting IRAKs might be one way that celastrol inhibits NF-κB. This is because IRAKs are key molecules for some crucial pathways to activate NF-κB (e.g., the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily).
METHODSThe human hepatocellular cell line (HepG2) treated with palmitic acid (PA) was used as a model for stimulating TLR4/NF-κB activation, in order to observe the potential effects of celastrol in IRAK regulation and NF-κB inhibition. The transfection of small interfering RNA was used for down-regulating TLR4, IRAK1 and IRAK4, and the Western blot method was used to detect changes in the protein expressions.
RESULTSThe results showed that celastrol could effectively inhibit PA-caused TLR4-dependent NF-κB activation in the HepG2 cells; PA also activated IRAKs, which were inhibited by celastrol. Knocking down IRAKs abolished PA-caused NF-κB activation.
CONCLUSIONThe results for the first time show that targeting IRAKs is one way in which celastrol inhibits NF-κB activation.