4.7 Article

Tryptophan Promotes Intestinal Immune Defense through Calcium-Sensing Receptor (CaSR)-Dependent Metabolic Pathways

期刊

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 69, 期 45, 页码 13460-13473

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c05820

关键词

improving tryptophan; defensin; calcium-sensing receptor; tryptophan metabolism; intestinal immune defense

资金

  1. National Natural Science Foundation of China [32030101, 31872368]
  2. Natural Science Foundation of Heilongjiang Province [TD2019C001]
  3. China Agriculture Research System of MOF and MARA

向作者/读者索取更多资源

Tryptophan regulates intestinal immunity by promoting the expression of AMPs, specifically pBD1 and pBD2, through the CaSR-tryptophan metabolic pathways. Moreover, tryptophan alleviates intestinal inflammation induced by LPS both in vitro and in vivo by activating the CaSR-AMPK pathways, and maintaining kynurenine homeostasis during the inflammatory response.
The gastrointestinal tract forms a robust line of defense against invading pathogens through the production of endogenous antimicrobial peptides (AMPs), which are crucial molecules of the innate defense system. Tryptophan could modulate intestinal immunity through promoting the expression of AMPs. However, the precise mechanism needs to be further clarified. In this study, we show that treatment with tryptophan for 24 h triggers (p < 0.05) the expression of porcine beta-defensin (pBD) 1 (62.67 +/- 3.10 pg/mL) and pBD2 (74.41 +/- 1.33 pg/mL) in the porcine intestinal epithelial cells (IPEC-J2) though calcium-sensing receptor (CaSR)-tryptophan metabolic pathways. Meanwhile, tryptophan alleviates (p < 0.05) intestinal inflammation induced by lipopolysaccharide (LPS) through induction of the defensins and activation of the CaSR-AMP-activated protein kinase (AMPK) pathways in vitro and in vivo. Moreover, the activation of CaSR induces the expression of defensins and decreases the levels of IL-1 beta (75.26 +/- 2.74 pg/mL) and TNF-alpha (449.8 +/- 23.31 pg/mL) induced by LPS (p < 0.05). Importantly, tryptophan maintains kynurenine homeostasis through the activation of CaSR during the inflammatory response. To that end, the work identifies a regulatory circuit between CaSR signaling and tryptophan metabolic pathways involved in the tryptophan-trigged AMP expression, which contributes to improving intestinal immune defense.

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