Tryptophan alleviates intestinal damage through regulating necroptosis and TLR4/NOD signaling pathways in pigs after lipopolysaccharide challenge

Abstract

This study aimed to test the hypothesis that necroptosis, toll-like receptor 4 (TLR4)/nucleotide-binding oligomerization domain (NOD) signaling pathway in the jejunum of lipopolysaccharide (LPS)-challenged piglets are involved in the alleviation of intestinal injury and inflammation by tryptophan supplementation. Tryptophan supplementation has improved intestinal morphology. Also, tryptophan has been found to increase the mRNA and protein expression of tight junction proteins and decrease the expression of pro-inflammatory cytokines. Dietary tryptophan decreased the mRNA expression of heat shock protein 70, TLR4, NOD1, NOD2, myeloid differentiation primary response gene 88, interleukin 1 receptor-associated kinase 1, TNF receptor-associated factor 6, receptor-interacting serine/threonine-protein kinase 2-like, nuclear factor-kappaB transcription factor P65 in the jejunum of piglets. Tryptophan alleviated LPS-induced necroptosis and decreased the mRNA expression of mixed lineage kinase domain-like, receptor-interacting serine/threonine kinase 1, receptor-interacting serine/threonine-protein kinase 3-like, Fas (TNFRSF6)-associated via death domain, PGAM family member 5. Collectively, our results suggest that tryptophan supplementation helps in the attenuation of intestinal injury and inflammation by alleviating necroptosis and TLR4/NOD in lipopolysaccharide-challenged pigs.

Keywords:

• Tryptophan
• tight junction
• inflammatory response
• necroptosis
• piglets

Acknowledgements

The authors would like to thank the members of our team and the laboratory for their industrious assistance in this experiment.

Ethical approval

The research protocol was carried out according to the Chinese Guidelines for Animal Welfare and Experimental Protocol and was approved by Sichuan Agricultural University Animal Care and Use Committee.

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The author agrees to publish.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The original contributions presented in this study are included in the article. Further inquiries can be directed the corresponding author.

Additional information

Funding

This project was supported by the Sichuan Science and Technology Program (No. 2020YJ0398) and Specific Research Supporting Program for Discipline Construction in Sichuan Agricultural University (No. 03570126).