J Immunol 1996,
PMID: 8906816
Singh, S; Natarajan, K; Aggarwal, B B
Viral replication, immune regulation, and induction of various inflammatory and growth-regulatory genes require activation of a nuclear transcription factor (NF)-kappa B. Agents that can block NF-kappa B activation have potential to block downstream responses mediated through this transcription factor. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a quinone that has been shown to regulate a wide variety of activities that require NF-kappa B activation. In the present study, we examined the effect of capsaicin and its analogue, resiniferatoxin, on the activation of NF-kappa B induced by different agents including TNF. The pretreatment of human myeloid ML-1a cells with capsaicin blocked TNF-mediated activation of NF-kappa B in a dose- and time-dependent manner. Resiniferatoxin was at least eight times as potent as capsaicin in inhibiting NF-kappa B activation. Neither agent by itself activated NF-kappa B or affected the DNA-binding ability of NF-kappa B. Capsaicin also blocked phorbol ester-mediated NF-kappa B activation, but that mediated through okadaic acid was less effective, suggesting there is a difference in the mechanism of activation of NF-kappa B by different agents. Capsaicin treatment of cells also blocked the degradation of I kappa B alpha, and thus the nuclear translocation of the p65 subunit of NF-kappa B, which is essential for NF-kappa B activation. TNF-dependent promoter activity of I kappa B alpha, which contains NF-kappa B binding sites, was also inhibited by capsaicin. Overall our results indicate that capsaicin and its analogue inhibit NF-kappa B activation, and thus could be used as a potential target for drug development.
Diseases/Pathways annotated by Medline MESH: Leukemia, Myelomonocytic, Acute
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Text Mining Data
transcription factor → NF)-kappa B: "
Viral replication, immune regulation, and induction of various inflammatory and growth-regulatory genes require
activation of a nuclear
transcription factor (
NF)-kappa B
"
NF-kappa B → TNF: "
The pretreatment of human myeloid ML-1a cells with capsaicin blocked TNF mediated activation of NF-kappa B in a dose- and time dependent manner
"
I kappa B alpha → TNF: "
TNF dependent promoter activity of I kappa B alpha , which contains NF-kappa B binding sites, was also inhibited by capsaicin
"
Manually curated Databases
No curated data.