The potent immunomodulatory compound VGX-1027 regulates inflammatory mediators in CD4 + T cells, which are concomitant with the prevention of neuroimmune dysregulation in BTBR T + Itpr3 tf /J mice.

Autor: Ahmad SF; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fashaikh@ksu.edu.sa., Nadeem A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Ansari MA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Bakheet SA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alasmari F; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alasmari AF; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Al-Kharashi LA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Al-Qahtani QH; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Attia SM; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2019 Nov 15; Vol. 237, pp. 116930. Date of Electronic Publication: 2019 Oct 11.
DOI: 10.1016/j.lfs.2019.116930
Abstrakt: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by symptoms that include social communication impairments, interaction deficits, and repetitive and stereotyped behaviors. Recent studies have suggested that imbalanced cytokine levels are associated with impaired behavioral outcomes in individuals with ASD. VGX-1027 is a potent immunomodulatory compound that has shown promise for the treatment of several neuroinflammatory disorders. Here, we studied the effects of VGX-1027 on BTBR T + Itpr3 tf /J (BTBR) mice, an animal model of autism. BTBR mice exhibit most of the core behavioral features of ASD, such as reduced sociability and increased repetitive behaviors. In this study, we investigated the effects of VGX-1027 on self-grooming, marble burying and sociability tests using BTBR mice. We further examined its effect on IL-1β, IL-6, IL-10, TNF-α, IFN-γ, and NF-κB p65 production in splenic CD4 + cells and on IL-1β, IL-6, IL-10, TNF-α, IFN-γ, COX-2, and iNOS (NOS2) protein and mRNA expression in brain tissues. The administration of VGX-1027 was found to attenuate self-grooming and marble burying behaviors, and enhance social interactions in BTBR mice. Additionally, VGX-1027 treatment resulted in a substantial decrease in IL-1β, IL-6, TNF-α, IFN-γ, and NF-κB p65 production, but increased IL-10 production in CD4 + T cells. Moreover, this agent was also found to significantly decrease IL-1β, IL-6, TNF-α, IFN-γ, COX-2, and NOS2 levels and increase IL-10 expression at the protein and mRNA level in brain tissues. Based on results using BTBR mice, our data provide the first evidence that VGX-1027 could potentially be used for the amelioration of autism-like symptoms.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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