title: IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro.
abstract: Interleukin-4 (IL-4) is a pleiotropic cytokine that regulates several phenomena, among them survival and differentiation of neuronal and glial cells. The aim of this work was to investigate the effect of IL-4 on the cholinergic differentiation of neonatal rat retinal cells in vitro, evaluating its effect on the levels of cholinergic markers (CHT1-high-affinity choline transporter; VAChT-vesicular acetylcholine transporter, ChAT-choline acetyltransferase, AChE-acetylcholinesterase), muscarinic receptors, and on the signaling pathways involved. Lister Hooded rat pups were used in postnatal days 0-2 (P0-P2). Our results show that IL-4 treatment (50 U/mL) for 48 h increases the levels of the cholinergic transporters VAChT and CHT1, the acetylcholinesterase activity, and the number of ChAT-positive cells. It also induces changes in muscarinic receptor levels, leading to a small decrease in M1 levels and a significant increase in M3 and M5 levels after 48 h of treatment. We also showed that IL-4 effect on M3 receptors is dependent on type I IL-4 receptor and on an increase in NFκB phosphorylation. These results indicate that IL-4 stimulates cholinergic differentiation of retinal cells.
authors: Programa de Neurociências, Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista s/n -Campus Valonguinho. Centro - Niterói, Rio de Janeiro, CEP: 24020-140, Brazil.
authors: Marcelo Gomes
authors: MG
authors: Granja
authors: Luis Eduardo Gomes
authors: LE
authors: Braga
authors: Raul
authors: R
authors: Carpi-Santos
authors: Leandro
authors: L
authors: de Araujo-Martins
authors: Nilson
authors: N
authors: Nunes-Tavares
authors: Karin C
authors: KC
authors: Calaza
authors: Aline Araujo
authors: AA
authors: Dos Santos
authors: Elizabeth
authors: E
authors: Giestal-de-Araujo
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000166:cytology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D053616:Janus Kinase 3 / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D026901:Membrane Transport Proteins; D016328:NF-kappa B; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D050494:Vesicular Acetylcholine Transport Proteins; C065637:choline transporter; D015847:Interleukin-4; D002217:Carbachol; D002795:Choline O-Acetyltransferase; D053616:Janus Kinase 3; D000110:Acetylcholinesterase