L-Leucine Promotes STAT1 and ISGs Expression in TGEV-Infected IPEC-J2 Cells
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Cell Line
Cells, Cultured
Gastroenteritis, Transmissible, of Swine
Gene Expression Regulation
/ drug effects
Host-Pathogen Interactions
/ genetics
Interferon Type I
/ metabolism
Leucine
/ pharmacology
Models, Biological
Protein Kinase Inhibitors
/ pharmacology
STAT1 Transcription Factor
/ genetics
Signal Transduction
/ drug effects
Swine
TOR Serine-Threonine Kinases
/ metabolism
Transmissible gastroenteritis virus
/ physiology
Virus Replication
IPEC-J2 cells
L-leucine
mammalian target of rapamycin
signal transducer and activator of transcription 1
transmissible gastroenteritis virus
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
21
01
2021
accepted:
30
06
2021
entrez:
9
8
2021
pubmed:
10
8
2021
medline:
30
9
2021
Statut:
epublish
Résumé
L-leucine (Leu), as one of the effective amino acids to activate the mTOR signaling pathway, can alleviate transmissible gastroenteritis virus (TGEV) infection. However, the underlying mechanism by which Leu alleviates the virus infection has not been fully characterized. In particular, how Leu impacts TGEV replication through mTOR signaling has yet to be elucidated. In the present study, we found that TGEV proliferated efficiently in intestinal porcine epithelial cells (IPEC-J2 cells) as evidenced by the increase in viral contents by flow cytometry, the inhibition of cell proliferation by CCK-8 assay as well as the reduction of PCNA level by western blot. Besides, western blot analysis showed that STAT1 expression was markedly reduced in TGEV-infected cells. The results of ELISA revealed the inhibition of ISGs (ISG56, MxA, and PKR) expressions by TGEV infection. TGEV-induced mTOR and its downstream p70 S6K and 4E-BP1, STAT1 and ISGs downregulation were blocked by an mTOR activator-MHY1485 but not by an mTOR inhibitor-RAPA. Concurrently, mTOR activation by MHY1485 reduced the contents of TGEV and vice versa. Furthermore, Leu reversed the inhibition of STAT1 and ISGs by activating mTOR and its downstream p70 S6K and 4E-BP1 in TEGV-infected cells. Our findings demonstrated that Leu promoted the expressions of STAT1 and ISGs
Identifiants
pubmed: 34367129
doi: 10.3389/fimmu.2021.656573
pmc: PMC8339710
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Interferon Type I
0
Protein Kinase Inhibitors
0
STAT1 Transcription Factor
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Leucine
GMW67QNF9C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
656573Informations de copyright
Copyright © 2021 Du, Chen, Yu, He, Yu, Mao, Luo, Zheng and Luo.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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