Essential amino acid tryptophan inhibits induction of inducible nitric oxide synthase gene expression in interleukin-1β stimulated hepatocytes
DOI:
https://doi.org/10.31989/bchd.v2i7.639Öz
Background: Tryptophan exerts protective effects against a variety of organ inflammation and injury, including the liver. However, there are few scientific reports about the mechanisms involved with the action. Pro-inflammatory cytokine interleukin (IL)-1β stimulates the induction of inducible nitric oxide synthase (iNOS) expression and NO production in cultured hepatocytes (“in vitro liver injury model”). Additionally, the prevention of iNOS expression and NO production is an indicator of liver protection. Thus, the study aimed to examine whether tryptophan influences the induction of iNOS gene expression and the mechanisms.
Methods: Tryptophan was added into primary cultures of rat hepatocytes stimulated by IL-1β. The iNOS induction, NO production, and its signaling pathway were analyzed.
Results: IL-1β induced iNOS gene expression, which was followed by iNOS expression and NO production. Tryptophan inhibited the expression of iNOS mRNA and protein, in addition to decreasing the production of NO. Transfection experiments with iNOS promoter-luciferase constructs revealed that tryptophan reduced the activities of iNOS mRNA synthesis and its stability. Tryptophan blocked two essential signaling pathways, the activation of nuclear factor (NF)-κB and upregulation of type I IL-1receptor (IL-1RI).
Conclusions: Results indicate that tryptophan can prevent the NO production by inhibition of iNOS gene expression, partly through NF-κB activation and IL-1RI upregulation in inflamed hepatocytes. Tryptophan may be a potential therapeutic treatment in injured organs, including the liver.
Keywords: tryptophan, inducible nitric oxide synthase, nitric oxide, cultured hepatocytes, nuclear factor-κB, type I interleukin-1 receptor
Yayınlanmış
Sayı
Bölüm
Lisans
Authors retain the copyright of their articles and grant the Functional Food Center (FFC) and its journals the right of first publication under the terms of the Creative Commons Attribution 4.0 International License.
This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged.
By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained.