Back to Search
Start Over
L-Threonine upregulates the expression of β-defensins by activating the NF-κB signaling pathway and suppressing SIRT1 expression in porcine intestinal epithelial cells.
- Source :
-
Food & function [Food Funct] 2021 Jul 05; Vol. 12 (13), pp. 5821-5836. - Publication Year :
- 2021
-
Abstract
- The use of antimicrobial peptide (AMP), found in all forms of life and playing a pivotal role in the innate immune system, has been developed as a new strategy for maintaining intestinal health and reducing antibiotic usage due to its ability to resist pathogens and commensal microbes. The current study investigated the effects of l-threonine on β-defensin expression, the intestinal mucosal barrier and inflammatory cytokine expression in porcine intestinal epithelial cell lines (IPEC-J2). The results revealed that in IPEC-J2 cells, l-threonine significantly increased the expression of β-defensin (including pBD-1, pBD-2, and pBD-3) in a dose- and time-dependent manner (P < 0.05). By using different concentrations and treatment times of l-threonine, the results showed that the expression of β-defensin was upregulated to the greatest extent in IPEC-J2 cells cultured with 1 mM l-threonine for 24 h. Although the mRNA expression levels of β-defensins were markedly increased (P < 0.05), there was relatively little inducible pBD-1, pBD-2 and pBD-3 mRNA expression at the sub-confluent and confluent densities in comparison with post-confluent densities. Furthermore, we found that l-threonine enhanced the β-defensin expression by suppressing the expression of SIRT1, which increased acetylated p65 expression, and activating the NF-κB signaling pathway, which induced the translocation of p65 from the cytoplasm to the nucleus. In addition, l-threonine significantly prevented LPS-induced intestinal mucosal barrier damage by attenuating the decreasing tendency of the mRNA expression of Mucin1 and Mucin2 (P < 0.05). Simultaneously, l-threonine enhanced the expression of β-defensins upon LPS challenge in IPEC-J2 cells (P < 0.05). l-Threonine obviously decreased the mRNA expression of inflammatory cytokines compared to that in untreated cells (P < 0.05). In conclusion, l-threonine can upregulate β-defensin expression and reduce inflammatory cytokine expression in IPEC-J2 cells; meanwhile, l-threonine alleviates LPS-induced intestinal mucosal barrier damage in porcine intestinal epithelial cells. The l-threonine-mediated modulation of endogenous defensin expression may be a promising approach to reduce antibiotic use, enhance disease resistance and intestinal health in animals.
- Subjects :
- Animals
Cell Line
Cytokines genetics
Cytokines metabolism
Gene Expression Regulation drug effects
Intestinal Mucosa metabolism
NF-kappa B genetics
Neoplasm Proteins
Nucleocytoplasmic Transport Proteins
RNA, Messenger metabolism
Sirtuin 1 genetics
Swine
Threonine metabolism
beta-Defensins genetics
Epithelial Cells drug effects
Intestines drug effects
NF-kappa B metabolism
Signal Transduction drug effects
Sirtuin 1 metabolism
Threonine pharmacology
Up-Regulation drug effects
beta-Defensins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2042-650X
- Volume :
- 12
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Food & function
- Publication Type :
- Academic Journal
- Accession number :
- 34047325
- Full Text :
- https://doi.org/10.1039/d1fo00269d