IL-6, A1 and A2aR: a crosstalk that modulates BDNF and induces neuroprotection.
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.
Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista s/n, Niterói, Rio de Janeiro CEP: 24020-140, Brazil; Blizard Institute - Queen Mary, University of London, 4 Newark St, London, City of London, Greater London E1 2AT, United Kingdom. Electronic address: rafaelperigolo@gmail.com.
Rafael
R
Perígolo-Vicente
Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista s/n, Niterói, Rio de Janeiro CEP: 24020-140, Brazil.
Karen
K
Ritt
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Av. Brasil, n° 4365, Manguinhos, CEP: 21045-900 Rio de Janeiro, RJ, Brazil.
Cassiano Felippe
CF
Gonçalves-de-Albuquerque
Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Av. Brasil, n° 4365, Manguinhos, CEP: 21045-900 Rio de Janeiro, RJ, Brazil.
Hugo Caire
HC
Castro-Faria-Neto
Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista s/n, Niterói, Rio de Janeiro CEP: 24020-140, Brazil.
Roberto
R
Paes-de-Carvalho
Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista s/n, Niterói, Rio de Janeiro CEP: 24020-140, Brazil.
Elizabeth
E
Giestal-de-Araujo
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D015850:Interleukin-6; D018696:Neuroprotective Agents; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C017759:9-(tetrahydro-2-furyl)-adenine; C027513:N(6)-cyclohexyladenosine; D000225:Adenine; D000241:Adenosine
Adenosine receptors; Axotomy; BDNF; Cell culture; Neuronal death; Retina