PMA treatment fosters rat retinal ganglion cell survival via TNF signaling

dc.creatorFerreira, Érica Camila
dc.creatorOliveira, Amanda Candida da Rocha
dc.creatorGarcia, Carlos Gustavo
dc.creatorCossenza, Marcelo
dc.creatorAlbuquerque, Cassiano Felippe Gonçalves de
dc.creatorFaria Neto, Hugo Caire Castro
dc.creatorAraujo, Elizabeth Giestal de
dc.creatorSantos, Aline Araujo dos
dc.date2021-11-06T19:56:54Z
dc.date2021-11-06T19:56:54Z
dc.date2021
dc.date.accessioned2023-09-26T20:45:39Z
dc.date.available2023-09-26T20:45:39Z
dc.identifierFERREIRA, Érica Camila et al. PMA treatment fosters rat retinal ganglion cell survival via TNF signaling. Neuroscience Letters, v. 763, 136197, p. 1-9, Aug. 2021.
dc.identifier0304-3940
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/49715
dc.identifier10.1016/j.neulet.2021.136197
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8863388
dc.descriptionAn 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.
dc.description2023
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectSobrevivência neuronal
dc.subjectCitocinas inflamatórias
dc.subjectPKC
dc.subjectRetina
dc.subjectTNF-a
dc.subjectIL-1B
dc.subjectNeuronal survival
dc.subjectInflammatory cytokines
dc.subjectPKC
dc.subjectRetina
dc.subjectTNF-a
dc.subjectIL-1B
dc.titlePMA treatment fosters rat retinal ganglion cell survival via TNF signaling
dc.typeArticle


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