Sholl-Franco Alfred, Marques Patrícia M B, Ferreira Cecília M C, de Araujo Elizabeth G
Departamento de Neurobiologia, Programa de Neuroimunologia, Instituto de Biologia, Centro de Estudos Gerais, Universidade Federal Fluminense, CP# 100180, RJ 24001-970, RJ, Niterói, Brazil.
J Neuroimmunol. 2002 Dec;133(1-2):20-9. doi: 10.1016/s0165-5728(02)00327-2.
Interleukin-4 (IL-4) is an anti-inflammatory cytokine. During injuries, infections and neurodegenerative diseases, high levels of this molecule are expressed in the brain. In the present work, we investigated the effect of IL-4 on GABAergic differentiation of retinal cells kept in vitro. We analyzed either the uptake of [3H]-gamma-aminobutyric acid (GABA) or the expression of glutamic acid decarboxylase (GAD-67) following IL-4 treatment. We have also investigated the pharmacological modulation of the [3H]-GABA uptake by cholinergic activation. Our results demonstrate that IL-4 increases the uptake of [3H]-GABA after 48 h in culture in a dose-dependent manner (0.5-100 U/ml). The maximal effect was obtained with 5 U/ml (75% increase). This effect was blocked by 1 mM of nipecotic acid, demonstrating the involvement of the GAT-1 subtype of GABA transporter. The IL-4 effect depends on M1 muscarinic activity, an increase in intracellular calcium levels, tyrosine kinase activity and protein kinase C (PKC) activity. Treatment with IL-4 for 48 h induced an increase of 90% in the number of GAD- and GABA-immunoreactive cells when compared with control cultures. Our results indicate that IL-4 modulates the GABAergic phenotype of retinal cells in culture. This result can suggest an important role for this cytokine either during the normal development of retinal circuitry or during neuroprotection after injuries.
白细胞介素-4（IL-4）是一种抗炎细胞因子。在损伤、感染和神经退行性疾病期间，大脑中会表达高水平的这种分子。在本研究中，我们调查了IL-4对体外培养的视网膜细胞GABA能分化的影响。我们分析了IL-4处理后[3H] -γ-氨基丁酸（GABA）的摄取或谷氨酸脱羧酶（GAD-67）的表达。我们还研究了胆碱能激活对[3H] -GABA摄取的药理学调节作用。我们的结果表明，培养48小时后，IL-4以剂量依赖性方式（0.5 - 100 U/ml）增加[3H] -GABA的摄取。5 U/ml时获得最大效应（增加75%）。1 mM的哌啶酸可阻断此效应，表明GABA转运体的GAT-1亚型参与其中。IL-4的作用取决于M1毒蕈碱活性、细胞内钙水平的升高、酪氨酸激酶活性和蛋白激酶C（PKC）活性。与对照培养物相比，用IL-4处理48小时可使GAD和GABA免疫反应性细胞数量增加90%。我们的结果表明，IL-4调节培养的视网膜细胞的GABA能表型。这一结果提示该细胞因子在视网膜回路的正常发育过程中或损伤后的神经保护过程中可能发挥重要作用。
