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.