IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

• Published in: Cellular and molecular neurobiology 2015-07, Vol.35 (5), p.689-701
• Main Authors: Granja, Marcelo Gomes, Braga, Luis Eduardo Gomes, Carpi-Santos, Raul, de Araujo-Martins, Leandro, Nunes-Tavares, Nilson, Calaza, Karin C., dos Santos, Aline Araujo, Giestal-de-Araujo, Elizabeth
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; Animals; Animals, Newborn; Biomedical and Life Sciences; Biomedicine; Carbachol - pharmacology; Cell Biology; Cell Differentiation - drug effects; Cells, Cultured; Choline O-Acetyltransferase - metabolism; Cholinergic Neurons - cytology; Cyclic AMP Response Element-Binding Protein - metabolism; Humans; Interleukin-4 - pharmacology; Janus Kinase 3 - metabolism; Membrane Transport Proteins - metabolism; Neurobiology; Neurosciences; NF-kappa B - metabolism; Original Research; Rats; Receptors, Cholinergic - metabolism; Receptors, Muscarinic - metabolism; Retina - cytology; Signal Transduction - drug effects; Time Factors; Vesicular Acetylcholine Transport Proteins - metabolism
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-015-0164-z

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.