S1P Lyase Inhibition Increased Intestinal S1P, Disrupted the Intestinal Barrier and Aggravated DSS-Induced Colitis.

ABSTRACT:

Background

Sphingosine-1-phospate (S1P) receptor agonists (eg, ozanimod) desensitize migrating lymphocytes by irreversibly binding to S1P receptors (S1PR) and triggering their proteasomal degradation. Desensitized lymphocytes cannot sense S1P, therefore, halting lymphocyte recirculation. The S1P lyase (SPL) irreversibly degrades S1P and its inhibition disrupts the S1P gradient. We previously found that systemic SPL inhibitors induce central immunosuppression. Here, we examined whether SPL inhibition may attenuate colitis without systemic immunotoxicity.

Methods

We first analyzed SPL expression and localization in mice using qRT-PCR and immunohistochemistry. SPL inhibitors 4-deoxypyridoxine hydrochloride (DOP) and 2-acetyl-4-(tetrahydroxybutyl) imidazole (THI) were used to in

SUBMITTER: Kaur P 

PROVIDER: S-EPMC12758529 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature