Treatment in vitro of retinal cells with IL-4 increases the survival of retinal ganglion cells: the involvement of BDNF.
Interleukin 4 (IL-4) is a pleiotropic cytokine involved in many functions during the development as well as in adult life. Previous work from our group demonstrated, in vitro, that this interleukin is able to prevent rat retinal ganglion cells death after axotomy. The aim of the present study was to investigate the signaling pathways involved in this trophic effect, particularly the cAMP pathway and also to demonstrate the expression of IL-4 in retinas at different stages of post natal development. Our results show that the trophic effect of IL-4 on rat retinal ganglion cells is dependent on the activation of Janus Kinase 3, Protein Kinase A, c-Jun N-terminal Kinase and Tropomyosin related Kinase receptors, on the increase in intracellular calcium levels, on polypeptide release and on the endogenous Brain Derived Neurotrophic Factor (BDNF). We also observed that treatment with IL-4 enhances c-AMP response element binding and Mitogen Activated Protein Kinase phosphorylation and increases the expression of BDNF. Concerning the IL-4 expression our data show an increase in IL-4 levels during post natal development. Taken together our results demonstrate that the trophic effect of IL-4 on retinal ganglion cells of newborn rats is mediated by cAMP pathway and BDNF release.
Programa de Neurociências, Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista s/n, Niterói, Rio de Janeiro CEP 24020-140, Brazil.
Leandro
L
de Araujo-Martins
Raphael Monteiro
RM
de Oliveira
Gabriela Velozo Gomes
GV
dos Santos
Renata Cláudia Celestino
RC
dos Santos
Aline Araujo
AA
dos Santos
Elizabeth
E
Giestal de Araujo
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015847:Interleukin-4; D000242:Cyclic AMP; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one