Interleukin-4 blocks thapsigargin-induced cell death in rat rod photoreceptors: involvement of cAMP/PKA pathway.
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.
Adão-Novaes
Juliana
J
Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Guterres
Céulem de Cássia Belem
Cde C
da Silva
Ana Gabriela Ledo Santos
AG
Campello-Costa
Paula
P
Linden
Rafael
R
Sholl-Franco
Alfred
A
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000633:toxicity; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D019948:Receptors, Interleukin-4 / Q000187:drug effects / Q000378:metabolism; D012162:Retinal Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D019284:Thapsigargin; D012243:Rhodopsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases