The role of the sphingosine axis in immune regulation: A dichotomy in the anti-inflammatory effects between sphingosine kinase 1 and sphingosine kinase 2-dependent pathways.
Int J Immunopathol Pharmacol
; 35: 20587384211053274, 2021.
Article
in En
| MEDLINE
| ID: mdl-34789044
ABSTRACT
Background:
Sphingosine kinase has been identified as playing a central role in the immune cascade, being a common mediator in the cellular response to a variety of signals. The different effects of sphingosine kinase 1 and 2 (SphK1 and SphK2, respectively) activity have not been completely characterized.Aim:
To determine the different roles played by SphK1 and SphK2 in the regulation of immune-mediated disorders.Methods:
Nine groups of mice were studied. Concanavalin A (ConA) injection was used to induce immune-mediated hepatitis. Mice were treated with SphK1 inhibitor (termed SphK-I) and SphK2 inhibitor (termed ABC294640), prior to ConA injection, and effects of treatment on liver enzymes, subsets of T lymphocytes, and serum levels of cytokines were observed.Results:
While liver enzyme elevation was ameliorated by administration of SphK1 inhibitor, SphK2 inhibitor-treated mice did not show this tendency. A marked decrease in expression of CD25+ T-cells and Foxp+ T-cells was observed in mice treated with a high dose of SphK1 inhibitor. Alleviation of liver damage was associated with a statistically significant reduction of serum IFNγ levels in mice treated with SphK1 inhibitor and not in those treated with SphK2 inhibitor.Conclusions:
Early administration of SphK1 inhibitor in a murine model of immune-mediated hepatitis alleviated liver damage and inflammation with a statistically significant reduction in IFN-γ levels. The data support a dichotomy in the anti-inflammatory effects of SphK1 and SphK2, and suggests that isoenzyme-directed therapies can improve the effect of targeting these pathways.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphotransferases (Alcohol Group Acceptor)
/
Hepatitis, Animal
/
Anti-Inflammatory Agents
Limits:
Animals
Language:
En
Journal:
Int J Immunopathol Pharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
PATOLOGIA
Year:
2021
Type:
Article