Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation
Cytokine, ISSN: 1043-4666, Vol: 42, Issue: 2, Page: 265-276
2008
- 64Citations
- 50Captures
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Metrics Details
- Citations64
- Citation Indexes64
- 64
- CrossRef51
- Captures50
- Readers50
- 50
Article Description
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-α was suppressed in the presence of carnosine (β-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 (β-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.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S104346660800046X; http://dx.doi.org/10.1016/j.cyto.2008.02.011; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=43049156413&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/18397832; https://linkinghub.elsevier.com/retrieve/pii/S104346660800046X; https://dx.doi.org/10.1016/j.cyto.2008.02.011
Elsevier BV
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