Pharmacological inhibition of soluble epoxide hydrolase attenuates chronic experimental autoimmune encephalomyelitis by modulating inflammatory and anti-inflammatory pathways in an inflammasome-dependent and -independent manner.

Inflammopharmacology
Merve BiliktuBahar Tunctan

Abstract

We aimed to determine the effect of soluble epoxide hydrolase (sEH) inhibition on chronic experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), associated with changes in inflammasome-dependent and -independent inflammatory and anti-inflammatory pathways in the CNS of mice. C57BL/6 mice were used to induce chronic EAE by using an injection of MOG35-55 peptide/PT. Animals were observed daily and scored for EAE signs for 25 days after immunization. Following the induction of EAE, the scores were increased after 9 days and reached peak value as determined by ≥ 2 or ≤ 3 with 8% mortality rate on day 17. On day 17, mice were administered daily PBS, DMSO, or TPPU (a potent sEH inhibitor) (1, 3, or 10 mg/kg) until the end of the study. TPPU only at 3 mg/kg dose decreased the AUC values calculated from EAE scores obtained during the disease compared to EAE and vehicle control groups. On day 25, TPPU also caused an increase in the PPARα/β/γ and NLRC3 proteins and a decrease in the proteins of TLR4, MyD88, NF-κB p65, p-NF-κB p65, iNOS/nNOS, COX-2, NLRC4, ASC, caspase-1 p20, IL-1β, caspase-11 p20, NOX subunits (gp91phox and p47phox), and nitrotyrosine in addition to 14,15-DHET and IL-1β levels compare...Continue Reading

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Citations

Jun 17, 2020·Multiple Sclerosis : Clinical and Laboratory Research·Hanie Yavarpour-Bali, Maryam Ghasemi-Kasman
Jan 8, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jiasi WuXianli Meng

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