Suppression of IL-8 gene transcription by resveratrol in phorbol ester treated human monocytic cells.
Resveratrol (3,4',5-trihydroxy-trans-silbene), a natural phytoalexin found in grapes and other food products, has promising anti-inflammatory and anticancer effects. To observe the modulation of interleukin-8 (IL-8) production in human monocytic cells by resveratrol and explore its mechanism at the gene transcription level, U937 cells were stimulated with phorbol 12-myristate 13-acetate (PMA) for 24h. IL-8 protein in supernatants was measured by radioimmunoassay. The cytotoxicity of PMA, dexamethasone and resveratrol was accessed by MTT cell proliferation assay. The RNA level of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and IL-8 were detected by RT-PCR using specific primers. DNA binding activities of NF-kappaB and AP-1 were examined by electrophoretic mobility shift assay (EMSA). 0.01-100 nM PMA could significantly induce IL-8 production in U937 cells; 10 microM Dexamethasone and 10, 1, 0.1 microM resveratrol could inhibit PMA-induced IL-8 protein production and mRNA accumulation. The cytotoxicity did not contribute to their inhibitory effect. The DNA binding activity of AP-1 was inhibited by dexamethasone and resveratrol, but resveratrol has little effect on PMA-induced NF-kappaB activation. Resveratrol could inhibit PMA-induced IL-8 production in U937 cells at protein and mRNA levels. The suppression of IL-8 gene transcription by resveratrol was, at least partly, due to inhibition of AP-1 activation.
Shen
Fang
F
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Chen
Su-Juan
SJ
Dong
Xiao-Jun
XJ
Zhong
Hui
H
Li
Yi-Tang
YT
Cheng
Gui-Fang
GF
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D020298:U937 Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016209:Interleukin-8; D016328:NF-kappa B; D013267:Stilbenes; D018808:Transcription Factor AP-1; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol