Protein kinases JAK and ERK mediate protective effect of interleukin-2 upon ganglion cells of the developing rat retina.
Interleukin-2 (IL-2), a prototypical pro-inflammatory cytokine firstly related to T cells differentiation, exerts pleiotrophic functions in several areas of the central nervous system. Previously we had described the neurotrophic roles of this interleukin upon retinal neurons. Therefore, the aim of this work was to investigate the signaling pathways involved in the neuroprotective effect of IL-2 on axotomized RGC. Herein we demonstrated that at postnatal day 2 IL-2 receptor α subunit (IL-2Rα) is expressed in inner plexiform layer, retinal ganglion cells layer and retinal nerve fibers layer. Moreover, using a model of organotypic retinal explants and rhodamine dextran retrograde labeling for specifically quantify RGC, we showed that IL-2 increased the survival of axotomized RGC after 2 (85.43±5.43%) and 5 (50.23%±5.32) days in vitro. Western blot analysis demonstrated that IL-2 treatment increased the phosphorilation of both extracellular signal-regulated kinases (ERK)1/2 and AKT (~two fold). However, its neuroprotective effect upon RGC was dependent of Janus kinase (JAK) and ERK1/2 activity but not of AKT activity. Taken together our results showed that the IL-2 neuroprotective action upon RGC in vitro is mediated by JAK and ERK1/2 activation.
Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-902Rio de Janeiro, RJ, Brazil.
Camila
C
Marra
Denise
D
Gomes Moret
Amanda
A
de Souza Corrêa
Fernanda
F
Chagas da Silva
Patrícia
P
Moraes
Rafael
R
Linden
Alfred
A
Sholl-Franco
D000818:Animals; D000831:Animals, Newborn; D007376:Interleukin-2 / Q000502:physiology*; D053613:Janus Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D012160:Retina / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*
D007376:Interleukin-2; D053613:Janus Kinase 1; D048052:Mitogen-Activated Protein Kinase 3