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...

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Bibliographic Details
Published in:	Neurochemical research Vol. 38; no. 1; pp. 162 - 173
Main Authors:	de Araujo-Martins, Leandro, de Oliveira, Raphael Monteiro, dos Santos, Gabriela Velozo Gomes, dos Santos, Renata Cláudia Celestino, dos Santos, Aline Araujo, Giestal de Araujo, Elizabeth
Format:	Journal Article
Language:	English
Published:	Boston Springer US 2013 Springer Nature B.V
Subjects:	Actins - metabolism Animals Axotomy Biochemistry Biomedical and Life Sciences Biomedicine Blotting, Western Brain-Derived Neurotrophic Factor - physiology Cell Biology Cell Count Cell Survival - drug effects Cells, Cultured Cyclic AMP - physiology Cyclic AMP Response Element-Binding Protein - metabolism Enzyme Activation - drug effects Enzyme Activation - physiology Enzyme Inhibitors - pharmacology Flavonoids - pharmacology Interleukin-4 - pharmacology Mitogen-Activated Protein Kinases - physiology Neurochemistry Neurology Neurosciences Original Paper Phosphorylation - physiology Protein Kinase C - antagonists & inhibitors Protein Kinase C - physiology Rats Retina - cytology Retina - drug effects Retina - transplantation Retinal Ganglion Cells - drug effects Signal Transduction - drug effects IL-4 Neuronal survival Cyclic AMP Retinal ganglion cells BDNF
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0364-3190 1573-6903
DOI:	10.1007/s11064-012-0904-0