PMID- 23070471 OWN - NLM STAT- MEDLINE DCOM- 20130529 LR - 20211021 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 38 IP - 1 DP - 2013 Jan TI - Treatment in vitro of retinal cells with IL-4 increases the survival of retinal ganglion cells: the involvement of BDNF. PG - 162-73 LID - 10.1007/s11064-012-0904-0 [doi] AB - 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. FAU - de Araujo-Martins, Leandro AU - de Araujo-Martins L AD - Programa de Neurociencias, Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de Sao Joao Batista s/n, Niteroi, Rio de Janeiro CEP 24020-140, Brazil. FAU - de Oliveira, Raphael Monteiro AU - de Oliveira RM FAU - dos Santos, Gabriela Velozo Gomes AU - dos Santos GV FAU - dos Santos, Renata Claudia Celestino AU - dos Santos RC FAU - dos Santos, Aline Araujo AU - dos Santos AA FAU - Giestal de Araujo, Elizabeth AU - Giestal de Araujo E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121016 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Actins) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 207137-56-2 (Interleukin-4) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Actins/metabolism MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*physiology MH - Cell Count MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cyclic AMP/physiology MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Enzyme Activation/drug effects/physiology MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/pharmacology MH - Interleukin-4/*pharmacology MH - Mitogen-Activated Protein Kinases/physiology MH - Phosphorylation/physiology MH - Protein Kinase C/antagonists & inhibitors/physiology MH - Rats MH - Retina/cytology/*drug effects/transplantation MH - Retinal Ganglion Cells/*drug effects MH - Signal Transduction/drug effects EDAT- 2012/10/17 06:00 MHDA- 2013/05/31 06:00 CRDT- 2012/10/17 06:00 PHST- 2012/05/02 00:00 [received] PHST- 2012/10/04 00:00 [accepted] PHST- 2012/07/24 00:00 [revised] PHST- 2012/10/17 06:00 [entrez] PHST- 2012/10/17 06:00 [pubmed] PHST- 2013/05/31 06:00 [medline] AID - 10.1007/s11064-012-0904-0 [doi] PST - ppublish SO - Neurochem Res. 2013 Jan;38(1):162-73. doi: 10.1007/s11064-012-0904-0. Epub 2012 Oct 16.