Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation

Cytokine. 2008 May;42(2):265-276. doi: 10.1016/j.cyto.2008.02.011. Epub 2008 Apr 7.


The enhanced intestinal production of pro-inflammatory cytokines leads to inflammation and carcinogenesis, and therefore its down-regulation by nutrients could represent a promising therapeutic approach. We found for the first time that the secretion of interleukin-8 (IL-8) in intestinal epithelial cells stimulated by hydrogen peroxide or TNF-alpha was suppressed in the presence of carnosine (beta-Ala-His), a dietary dipeptide. Interestingly, carnosine had no influence on the stimulus-induced IL-8 mRNA expression, although the intracellular production and secretion of IL-8 were significantly inhibited by carnosine. The inhibitory effect of carnosine on the IL-8 secretion differed from that of other histidine-containing dipeptides like Gly-His, Ala-His, and anserine (beta-Ala-1-methyl-His), which inhibited both the hydrogen peroxide-induced secretion and mRNA expression of IL-8. These observations indicate that carnosine inhibited IL-8 secretion along a unique pathway, in which IL-8 production was suppressed at a post-transcriptional level, for instance, translation. The hypothesis that carnosine inhibited the translation of IL-8 mRNA is supported by the finding that the phosphorylation of eIF4E, an initiation factor, in stimulated Caco-2 cells was inhibited by carnosine. These results suggest that carnosine is a novel type of anti-inflammatory agent that down-regulates the inflammatory response in intestinal epithelial cells by a unique mechanism.

MeSH terms

  • Caco-2 Cells
  • Carnosine / physiology*
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation / physiology*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*


  • Interleukin-8
  • Carnosine
  • Hydrogen Peroxide