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  • Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells.

Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells.

Virulence (2018-08-14)
Forrest Keck, Stephanie Kortchak, Allison Bakovic, Brian Roberts, Nitin Agrawal, Aarthi Narayanan
ABSTRACT

Venezuelan equine encephalitis virus (VEEV) is a neurotropic arbovirus that is highly infectious as an aerosol and can result in an encephalitic phenotype in infected individuals. VEEV infections are known to be associated with robust inflammation that eventually contributes to neurodegenerative phenotypes. In this study, we utilize the TC-83 strain of VEEV, which is known to induce the expression of IL-6, IL-8, and other pro-inflammatory cytokines. We had previously demonstrated that TC-83 infection resulted in changes in mitochondrial function, eventually resulting in mitophagy. In this manuscript, we provide data that links upstream mitochondrial dysfunction with downstream pro-inflammatory cytokine production in the context of microglia and astrocytoma cells. We also provide data on the role of bystander cells, which significantly contribute to the overall inflammatory load. Use of a mitochondrial-targeted antioxidant, mitoquinone mesylate, greatly reduced the inflammatory cytokine load and ameliorated bystander cell inflammatory responses more significantly than a broad-spectrum anti-inflammatory compound (BAY 11-7082). Our data suggest that the inflammatory mediators, especially IL-1β, may prime naïve cells to infection and lead to increased infection rates in microglial and astrocytoma cells. Cumulatively, our data suggest that the interplay between mitochondrial dysfunction and inflammatory events elicited in a neuronal microenvironment during a TC-83 infection may contribute to the spread of infection.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pentostatin, ≥95% (HPLC)
Sigma-Aldrich
L-(−)-Glucose, ≥99%
Sigma-Aldrich
Tetramethylrhodamine ethyl ester perchlorate, suitable for fluorescence, ≥90% (HPCE)