Glycyrrhizin Inhibits PEDV Infection and Proinflammatory Cytokine Secretion via the HMGB1/TLR4-MAPK p38 Pathway.
Animals
Cells, Cultured
Chlorocebus aethiops
Coronavirus Infections
/ veterinary
Glycyrrhizic Acid
/ pharmacology
HMGB1 Protein
/ metabolism
Porcine epidemic diarrhea virus
/ drug effects
Signal Transduction
/ drug effects
Swine
Swine Diseases
/ metabolism
Toll-Like Receptor 4
/ metabolism
Vero Cells
p38 Mitogen-Activated Protein Kinases
/ metabolism
HMGB1
MAPK p38
PEDV infection
TLR4
glycyrrhizin
proinflammatory cytokine
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
23 Apr 2020
23 Apr 2020
Historique:
received:
31
03
2020
revised:
13
04
2020
accepted:
14
04
2020
entrez:
29
4
2020
pubmed:
29
4
2020
medline:
30
1
2021
Statut:
epublish
Résumé
Our previous study showed that glycyrrhizin (GLY) inhibited porcine epidemic diarrhea virus (PEDV) infection, but the mechanisms of GLY anti-PEDV action remain unclear. In this study, we focused on the anti-PEDV and anti-proinflammatory cytokine secretion mechanisms of GLY. We found that PEDV infection had no effect on toll-like receptor 4 (TLR4) protein and mRNA levels, but that TLR4 regulated PEDV infection and the mRNA levels of proinflammatory cytokines. In addition, we demonstrated that TLR4 regulated p38 phosphorylation but not extracellular regulated protein kinases1/2 (Erk1/2) and c-Jun N-terminal kinases (JNK) phosphorylation, and that GLY inhibited p38 phosphorylation but not Erk1/2 and JNK phosphorylation. Therefore, we further explored the relationship between high mobility group box-1 (HMGB1) and p38. We demonstrated that inhibition of HMGB1 using an antibody, mutation, or knockdown decreased p38 phosphorylation. Thus, HMGB1 participated in activation of p38 through TLR4. Collectively, our data indicated that GLY inhibited PEDV infection and decreased proinflammatory cytokine secretion via the HMGB1/TLR4-mitogen-activated protein kinase (MAPK) p38 pathway.
Identifiants
pubmed: 32340172
pii: ijms21082961
doi: 10.3390/ijms21082961
pmc: PMC7215578
pii:
doi:
Substances chimiques
HMGB1 Protein
0
Toll-Like Receptor 4
0
Glycyrrhizic Acid
6FO62043WK
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 31902253
Organisme : Natural Science Foundation of Jiangsu Province
ID : BK20180921
Organisme : the individual technology research and development of modern agricultural industry of Jiangsu Province
ID : CX(19)3024
Organisme : China Postdoctoral Science Foundation
ID : 2018M632399
Organisme : Priority Academic Program Development of Jiangsu Higher Education Institutions
ID : PAPD
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