The anti-inflammatory activity of the polyphenol resveratrol may be partially related to inhibition of tumour necrosis factor-α (TNF-α) pre-mRNA splicing

The present study shows for the first time that the polyphenol resveratrol (RESV) blocks processing of tumour necrosis factor-α (TNF-α) pre-mRNA in mature mRNA. This study was carried out in turbot (Psetta maxima (L.)), a fish species that we are using to evaluate the effects of RESV on the inflammatory response in vertebrates. Treatment of turbot head kidney leucocytes with polysaccharides from the seaweed Ulva rigida (ulvan) resulted in an increase in TNF-α expression. RESV did not inhibit transcription but almost completely inhibited the production of mRNA in ulvan-induced cells and caused a notable increase in the level of unspliced TNF-α pre-mRNA. RESV also induced accumulation of IL-1β pre-mRNA at the expense of mature mRNA, although the effects on IL-1β were less evident than those on TNF-α. However, the housekeeping gene was not affected by RESV. We also evaluated the effects of RESV in vivo under an inflammatory stimulus and found an inhibitory effect on TNF-α and IL-1β pre-mRNA splicing in turbot head kidney at 24 and 48h post-injection. In addition, RESV also reduced migration of cells to the peritoneal cavity under the same inflammatory stimulus. The results show that this fish species may be a useful model for analysing the effects of RESV on TNF-α and IL-1β expression, and suggest that RESV could be used to decrease the levels of pro-inflammatory cytokines in vivo and to reduce inflammatory reactions in certain inflammatory diseases.