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
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.
Cell Mol Neurobiol. 2015 Jul;35(5):689-701. doi: 10.1007/s10571-015-0164-z. Epub 2015 Feb 15.
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.
白细胞介素-4(IL-4)是一种多效性细胞因子,可调节多种生理现象,包括神经元和神经胶质细胞的存活与分化。本研究旨在探讨IL-4对新生大鼠视网膜细胞胆碱能分化的影响,评估其对胆碱能标志物(CHT1 - 高亲和力胆碱转运体;VAChT - 囊泡乙酰胆碱转运体、ChAT - 胆碱乙酰转移酶、AChE - 乙酰胆碱酯酶)、毒蕈碱受体水平以及相关信号通路的作用。选用出生后0 - 2天(P0 - P2)的利斯特戴帽大鼠幼崽。我们的结果表明,48小时的IL-4处理(50 U/mL)可提高胆碱能转运体VAChT和CHT1的水平、乙酰胆碱酯酶活性以及ChAT阳性细胞的数量。它还会引起毒蕈碱受体水平的变化,导致处理48小时后M1水平略有下降,M3和M5水平显著升高。我们还表明,IL-4对M3受体的作用依赖于I型IL-4受体以及NFκB磷酸化的增加。这些结果表明,IL-4可刺激视网膜细胞的胆碱能分化。