Janus kinase inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice.
Acute hepatitis
Apoptosis
Inflammation
JAK
Tofacitinib
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
30
07
2022
accepted:
03
11
2022
pubmed:
13
12
2022
medline:
3
2
2023
entrez:
12
12
2022
Statut:
ppublish
Résumé
The Janus kinase (JAK) is a crucial intracellular signaling hub for numerous cytokines, which is extensively involved in the activation of inflammatory cascade and the induction of inflammatory injury. JAK inhibition provides protective effects in several inflammation-based disorders, but the potential effects of JAK inhibitor in inflammation-based acute hepatitis remain to be investigated. Acute hepatitis is induced by Lipopolysaccharide/D-galactosamine (LPS/D-Gal) in mice with or without the JAK inhibitor Tofacitinib administration. The degree of liver injury, the production of pro-inflammatory cytokines and induction of hepatocytes apoptosis were determined. The results indicated that treatment with Tofacitinib decreased the levels of aminotransferases, attenuated the histological abnormalities in liver and decreased the plasma levels of TNF-α and IL-6 in LPS/D-Gal-insulted mice. In addition, Tofacitinib suppressed the activation of the caspase cascade, decreased the level of cleaved caspase-3, and reduced the count of TUNEL-positive cells. Treatment with Tofacitinib alleviated LPS/D-Gal-induced acute hepatitis. JAK maybe become a promising target for the control of inflammation-based liver disorders.
Sections du résumé
BACKGROUND
BACKGROUND
The Janus kinase (JAK) is a crucial intracellular signaling hub for numerous cytokines, which is extensively involved in the activation of inflammatory cascade and the induction of inflammatory injury. JAK inhibition provides protective effects in several inflammation-based disorders, but the potential effects of JAK inhibitor in inflammation-based acute hepatitis remain to be investigated.
METHODS AND RESULTS
RESULTS
Acute hepatitis is induced by Lipopolysaccharide/D-galactosamine (LPS/D-Gal) in mice with or without the JAK inhibitor Tofacitinib administration. The degree of liver injury, the production of pro-inflammatory cytokines and induction of hepatocytes apoptosis were determined. The results indicated that treatment with Tofacitinib decreased the levels of aminotransferases, attenuated the histological abnormalities in liver and decreased the plasma levels of TNF-α and IL-6 in LPS/D-Gal-insulted mice. In addition, Tofacitinib suppressed the activation of the caspase cascade, decreased the level of cleaved caspase-3, and reduced the count of TUNEL-positive cells.
CONCLUSION
CONCLUSIONS
Treatment with Tofacitinib alleviated LPS/D-Gal-induced acute hepatitis. JAK maybe become a promising target for the control of inflammation-based liver disorders.
Identifiants
pubmed: 36507969
doi: 10.1007/s11033-022-08086-6
pii: 10.1007/s11033-022-08086-6
doi:
Substances chimiques
Janus Kinase Inhibitors
0
Lipopolysaccharides
0
tofacitinib
87LA6FU830
Galactosamine
7535-00-4
Cytokines
0
Tumor Necrosis Factor-alpha
0
Janus Kinases
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1477-1485Subventions
Organisme : National Natural Science Foundation of China
ID : No.81871606
Organisme : Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province
ID : No. KJQN201900435
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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