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J Neurosci Res ; 87(9): 2167-74, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19235892

ABSTRACT

Although the photoreceptors cell death is the main cause of some retinopathies diseases, the mechanisms involved in this process are poorly understood. The neuroprotective effects of interleukin-4 (IL-4) have been shown in several tissues, including retina. We demonstrate that treatment of rat retinal explants with IL-4 completely inhibited the thapsigargin-induced rod photoreceptor cell death after 24 hr in culture. We also showed that IL-4 receptor alpha subunit (IL-4Ralpha) is abundantly present in retina. Colocalization of IL-4Ralpha and rhodopsin indicate a direct effect of this cytokine in rod photoreceptor cells. Moreover, IL-4 increased the intracellular levels of cAMP in 7.4-fold, indicating that the neuroprotective effect of this cytokine was completely blocked by RpcAMP, an inhibitor of protein kinase (PKA). Our data demonstrate, for the first time, the neuroprotective effect of IL-4 through cAMP/PKA pathway in thapsigargin-induced photoreceptor cell death.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Interleukin-4/pharmacology , Neuroprotective Agents/pharmacology , Retinal Rod Photoreceptor Cells/drug effects , Animals , Cell Death/drug effects , Cell Death/physiology , Cyclic AMP/analogs & derivatives , Cytoprotection/drug effects , Cytoprotection/physiology , Enzyme Inhibitors/toxicity , Interleukin-4/metabolism , Nerve Degeneration/chemically induced , Nerve Degeneration/drug therapy , Nerve Degeneration/prevention & control , Neuroprotective Agents/metabolism , Organ Culture Techniques , Rats , Receptors, Interleukin-4/drug effects , Receptors, Interleukin-4/metabolism , Retinal Degeneration/drug therapy , Retinal Degeneration/metabolism , Retinal Degeneration/physiopathology , Retinal Rod Photoreceptor Cells/metabolism , Retinal Rod Photoreceptor Cells/pathology , Rhodopsin/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology , Thapsigargin/toxicity , Up-Regulation/drug effects , Up-Regulation/physiology
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