Diarylheptanoid hirsutenoxime inhibits toll-like receptor 4-mediated NF-κB activation regulated by Akt pathway in keratinocytes.
Microbial products, including lipopolysaccharides, may be involved in the pathogenesis of inflammatory skin diseases. We examined the effect of hirsutenoxime on the Toll-like receptor 4-mediated activation of Akt and nuclear factor (NF)-κB in lipopolysaccharide-stimulated keratinocytes. Hirsutenoxime, a cell signaling Akt inhibitor, and Bay 11-7085, an inhibitor of NF-κB activation, attenuated the lipopolysaccharide-induced expression of Toll-like receptor 4, activation of NF-κB and Akt, and the production of chemokines and reactive oxygen/nitrogen species. Hirsutenoxime may reduce the Toll-like receptor 4 expression-mediated NF-κB activation, which is regulated by the Akt pathway in keratinocytes exposed to lipopolysaccharides. This effect may reduce the skin inflammatory response.
Department of Pharmacology, Chung-Ang University, Seoul, South Korea.
Yun Jeong
YJ
Kim
Eun-Ra
ER
Jang
Jong Chan
JC
Lee
Seong Jun
SJ
Seo
Min Won
MW
Lee
Chung Soo
CS
Lee
D029661:Alnus / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D018925:Chemokines / Q000378:metabolism; D036381:Diarylheptanoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism*; D010091:Oximes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012871:Skin Diseases / Q000188:drug therapy* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
C557715:1,7-bis(3,4-dihydroxyphenyl)hept-4-en-3-one oxime; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018925:Chemokines; D036381:Diarylheptanoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010091:Oximes; D010936:Plant Extracts; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051057:Proto-Oncogene Proteins c-akt