PMA treatment fosters rat retinal ganglion cell survival via TNF signaling. (15th October 2021)

• Record Type: Journal Article
• Authors: Ferreira, Érica Camila; Oliveira, Amanda Candida da Rocha; Garcia, Carlos Gustavo; Cossenza, Marcelo; Gonçalves-de-Albuquerque, Cassiano Felippe; Castro-Faria-Neto, Hugo Caire; Giestal-de-Araujo, Elizabeth; dos Santos, Aline Araujo
• Is Part Of: Neuroscience letters. Volume 763(2021)
• Publication Date: 2021-10-15
• Subjects: PMA phorbol 12-myristate 13-acetate -- RGCs retinal ganglion cells -- TNFRI TNF receptor type I -- TNFRII TNF receptor type II -- ROS reactive oxygen species -- NO nitric oxide -- EthD1 ethidium homodimer-1 -- DD death domain -- TRAF TNF receptor associated factor -- NFkB nuclear transcription factor kappa B -- JNK c-Jun N-terminal Kinase -- MAPK mitogen-activated protein kinase -- PKC protein kinase C -- FCS fetal calf serum -- BSA bovine serum albumin -- CMF calcium and magnesium-free balanced salt solution -- DHE dihydroethidium -- DMSO dimethyl sulfoxide -- HRP horseradish peroxidase; Neuronal survival -- Inflammatory cytokines -- PKC -- Retina -- TNF-α -- IL-1β; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2021.136197
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: PKC activation modulates IL-1β and TNF-α release in rat retinal cells in culture. IL-1β and TNF-α are involved in RGCs survival mediated by PMA treatment. PMA decreases caspase 3 activation and ROS production in retinal cells culture. Abstract: An insult can trigger a protective response or even cell death depending on different factors that include the duration and magnitude of the event and the ability of the cell to activate protective intracellular signals, including inflammatory cytokines. Our previous work showed that the treatment of Lister Hooded rat retinal cell cultures with 50 ng/mL phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, increases the survival of retinal ganglion cells (RGCs) kept in culture for 48 h after axotomy. Here we aim to analyze how PMA modulates the levels of TNF-α and IL-1β (both key inflammatory mediators) and the impact of this modulation on RGCs survival. We hypothesize that the increase in RGCs survival mediated by PMA treatment depends upon modulation of the levels of IL-1β and TNF-α. The effect of PMA treatment was assayed on cell viability, caspase 3 activation, TNF-α and IL-1β release and TNF receptor type I (TNFRI) and TNF receptor type II (TNFRII) levels. PMA treatment increases IL-1β and TNF-α levels in 15 min in culture and increases the release of both cytokines after 30 min and 24 h, respectively. Both IL-1β and TNF-α levels decrease after 48 h of PMA treatment. PMA treatment also induces an increase in TNFRII levels while decreasing TNFRI after 24 h. PMA also inhibited caspase-3 activation, and decreased ROS production and EthD-1/calcein ratio in retinal cell cultures leading to an increase in cell viability. The neutralization of IL-1β (anti-IL1β 0, 1ng/mL), the neutralization of TNF-α (anti-TNF-α 0, 1ng/mL) and the TNF-α inhibition using a recombinant soluble TNFRII abolished PMA effect on RGCs survival. These data suggest that PMA treatment induces IL1β and TNF-α release and modulation of TNFRI/TNFRII expression promoting RGCs survival after axotomy.