Suppression of IL-8 gene transcription by resveratrol in phorbol ester treated human monocytic cells

Abstract

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.

SIRT1 Regulates CD40 Expression Induced by TNF-a via NF-?B Pathway in Endothelial Cells

“…other studies have revealed that resveratrol could inhibit IL-8 protein production induced by phorbol ester in human monocytic cells [29], and significantly decrease endothelin-1 and E-selectin mRNA expressions in high glucose cultured primary HUVECs [30]. In the present study, we also found that pretreatment with resveratrol attenuated CD40 expression induced by TNF-α in CRL-1730 endothelial cells.…”

Resveratrol as a Chemopreventive Agent: A Promising Molecule for Fighting Cancer

“…Various reports have demonstrated that eukaryotic transcription factor such as AP-1 or NFκB are involved in the regulation of COX-2. Resveratrol is able to reduce the DNA binding activity and transcriptional activities of nuclear factors [81,107,108] and subsequently decreases the transcriptional activity of COX-2 expression [106,109]. These results are also shown in vivo where administration of resveratrol is able to suppress NMBA-induced rat oesophageal tumorigenesis by targeting COXs and PGs production [58].…”

Resveratrol: Preventing properties against vascular alterations and ageing

“…Resveratrol inhibits the lipopolysaccharide (LPS)-induced expression of IL-1mRNA in monocytes and ECs [56]. Concerning IL-8, the gene transcription as well as the protein production are inhibited by resveratrol [57].…”