Tryptophan promoted β-defensin-2 expression via the mTOR pathway and its metabolites: kynurenine banding to aryl hydrocarbon receptor in rat intestine
Zhiru Tang RSC Advances Issue 6, 2020,
In this study, we investigated the signalling pathways mediating tryptophan (Trp)-promoted β-defensin-2 (BD-2) expression in rat intestinal mucosa. Sprague Dawley rats were administered with L-Trp and treated with rapamycin (RAPA), 1-methyltryptophan (1-MT), or para-chlorophenyl-amine (PCPA) to inhibit mammalian target of rapamycin (mTOR), indoleamine-2,3-dioxygenase (IDO), or tryptophan hydroxylase (TPH), respectively. The mRNA and protein levels of BD-2 in the jejunal and ileal mucosa of rats increased with administration of L-Trp. Intraperitoneal injection of RAPA significantly decreased the mRNA level of BD-2 and the concentrations of p-mTORC1 and BD-2 in the jejunal and ileal mucosa of rats with administration of L-Trp (P < 0.05). Oral administration of 1-MT decreased the IDO activity and the mRNA and protein levels of BD-2, and increased the concentrations of tumour necrosis factor (TNF-α), interleukin (IL)-17, and IL-22 in the jejunal and ileal mucosa of rats with administration of L-Trp (P < 0.05). Intraperitoneal injection of PCPA decreased the TPH activity and increased the mRNA and protein levels of BD-2, but did not change the concentrations of TNF-α, IL-17, or IL-22 in the jejunal and ileal mucosa of rats with administration of L-Trp.
The results indicate the Trp-promoted BD-2 expression in the jejunum and ileum via the mTOR pathway and its metabolites: kynurenine banding to aryl hydrocarbon receptor in rat intestine.
Introduction
Beta-defensin-2 (BD-2) plays a key role in the prevention of intestinal pathogenic microbial infection. The BD-2 expression is induced by infective stimuli, including Gram-negative and Gram-positive bacteria and their components or pro-inflammatory mediators, for example, tumour necrosis factor (TNF-α) and interleukin (IL)-1β.1–3
Amino acids (AAs) have been shown to play important roles in immune responses by regulating (1) the production of cytokines, antibodies and other cytotoxic substances;4,5 (2) gene expression, cellular redox state and lymphocyte proliferation; and (3) the activation of B and T lymphocytes, natural killer cells and macrophages. Studies have shown that dietary specific AA supplementation enhances the immune status of animals with malnutrition and infectious diseases, thereby reducing morbidity and mortality.6,7 Notably, tryptophan (Trp) is associated with many important immune functions. Dietary Trp supplementation improves the growth performance of piglets challenged by pathogenic Escherichia coli.8,9 Other studies have shown that Trp is useful in decreasing intestinal permeability and improving the intestinal barrier function.10 Hashimoto et al.11 reported that, Trp controls expression of small intestinal antimicrobial peptides (AMPs).
l-Trp plays important roles in protein synthesis and as a precursor of various bioactive compounds, such as kynurenine (Kyn) and 5-hydroxytryptamine (5-HT).12,13 Thus, l-Trp might promote the expression of BD-2 in the epithelial cells through the following pathways: (1) activating the mTOR pathway via its intracellular receptors thereby promoting the expression of BD-2; (2) promoting the expression of BD via Kyn, which is as a ligand of aryl hydrocarbon receptor (AhR) can promote intestinal epithelial cell secretion of IL-22, IL-17, and other cytokines that enhance the expression of BD-2 in the intestinal epithelial cells via the NF-κB pathway;14–16 or (3) promoting the expression of BD via 5-HT. In this study, Sprague Dawley rats were used to investigate the signalling pathways mediating Trp-promoted BD-2 expression in the rat intestinal mucosa.
