Peperomins as anti-inflammatory agents that inhibit the NF-kappaB signaling pathway.
The transcription factor nuclear factor kappaB (NF-kappaB) induces the expression of various inflammatory genes. In the common NF-kappaB signaling pathway, peperomin E and 2,6-didehydropeperomin B inhibited IkappaB degradation upon stimulation with TNF-alpha or interleukin-1. Consistent with these results, peperomin E and 2,6-didehydropeperomin B blocked the TNF-alpha-induced activation of IkappaB kinase, while they had no direct effect on the IkappaB kinase activity. Our present results clearly demonstrate that peperomins inhibit the NF-kappaB signaling pathway by blocking IkappaB kinase activation.
Tsutsui
Chieko
C
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Yamada
Yuriko
Y
Ando
Masayoshi
M
Toyama
Daisuke
D
Wu
Jian-Lin
JL
Wang
Liyan
L
Taketani
Shigeru
S
Kataoka
Takao
T
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D052117:Benzodioxoles / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007375:Interleukin-1 / Q000378:metabolism; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C545362:2,6-didehydropeperomin B; D000893:Anti-Inflammatory Agents; D052117:Benzodioxoles; D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C545363:peperomin E