Celastrol targets IRAKs to block Toll-like receptor 4-mediated nuclear factor-κB activation / 中西医结合学报
Journal of Integrative Medicine
;
(12): 203-208, 2016.
Artigo
em Inglês
| WPRIM
| ID: wpr-317031
ABSTRACT
<p><b>OBJECTIVE</b>Celastrol 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).</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>The results for the first time show that targeting IRAKs is one way in which celastrol inhibits NF-κB activation.</p>
Texto completo:
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Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Fosforilação
/
Fisiologia
/
Triterpenos
/
NF-kappa B
/
Receptor 4 Toll-Like
/
Quinases Associadas a Receptores de Interleucina-1
/
Células Hep G2
/
Metabolismo
Tipo de estudo:
Estudo prognóstico
Limite:
Humanos
Idioma:
Inglês
Revista:
Journal of Integrative Medicine
Ano de publicação:
2016
Tipo de documento:
Artigo
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