RESUMO
Several diseases are related to retinal ganglion cell death, such as glaucoma, diabetes and other retinopathies. Many studies have attempted to identify factors that could increase neuroprotection after axotomy of these cells. Interleukin-6 has been shown to be able to increase the survival and regeneration of retinal ganglion cells (RGC) in mixed culture as well as in vivo. In this work we show that the trophic effect of IL-6 is mediated by adenosine receptor (A2aR) activation and also by the presence of extracellular BDNF. We also show that there is a complex cross-talk between IL-6, BDNF, the Adenosine A1 and A2a receptors that results in neuroprotection of retinal ganglion cells.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Interleucina-6/fisiologia , Receptor A1 de Adenosina/fisiologia , Receptor A2A de Adenosina/fisiologia , Células Ganglionares da Retina/patologia , Adenina/análogos & derivados , Adenina/farmacologia , Adenosina/análogos & derivados , Adenosina/farmacologia , Animais , Axotomia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Fármacos Neuroprotetores/farmacologia , Fenetilaminas/farmacologia , Ratos , Receptor A1 de Adenosina/biossíntese , Receptor A2A de Adenosina/biossínteseRESUMO
IL-6 is a pleiotropic cytokine classically denominated pro-inflammatory. It has been already demonstrated that IL-6 can increase the survival of retinal ganglion cells (RGC) in culture. In this work, we show that the trophic effect of IL-6 is mediated by adenosine receptor (A1R) activation. The neutralization of extracellular BDNF abolished the IL-6 effect and the treatment with IL-6 and CHA (an agonist of A1R) modulated BDNF expression as well as pCREB and pTrkB levels.
