Effects of acanthoic acid on TNF-alpha gene expression and haptoglobin synthesis.
Tumour necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine inducing the synthesis and release of many inflammatory mediators. It is involved in immune regulation, autoimmune diseases, and inflammation. Our previous study demonstrated that acanthoic acid, (-)-pimara-9(11), 15-dien-19-oic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, inhibited TNF-alpha production. To extend our understanding of inhibitory effects of acanthoic acid on TNF-alpha production, its effects on TNF-alpha gene expression was tested. Based on the results from RT-PCR and promoter analysis of TNF-alpha, it was found that acanthoic acid suppressed TNF-alpha gene expression. But the same concentration of acanthoic acid had no effect on IL-6 gene expression. Haptoglobin is an acute phase protein which is induced by TNF-alpha. When liver cells were treated with acanthoic acid, haptoglobin synthesis was blocked by acanthoic acid. These data confirmed that acanthoic acid inhibited gene expression and biological function of TNF-alpha.
Kang
H S
HS
Immune Cell Signal Transduction Research Unit, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, Republic of Korea.
Song
H K
HK
Lee
J J
JJ
Pyun
K H
KH
Choi
I
I
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006242:Haptoglobins / Q000096:biosynthesis*; D006367:HeLa Cells; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D006242:Haptoglobins; D014409:Tumor Necrosis Factor-alpha; C099958:acanthoic acid