Nakazato Y, Hayashida T, Kanno Y, Sasamura H, Okada H, Suzuki H, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Saitama, Japan.
Kidney Int. 1998 Jul;54(1):71-9. doi: 10.1046/j.1523-1755.1998.00967.x.
While interleukin (IL)-4 inhibits pro-inflammatory cytokine expression by human monocytes, we have observed that it potentiates IL-6 production by IL-1-activated human mesangial cells (MC). To study the mechanism of this cell-type specific interaction between IL-1 and IL-4 in MC, we examined the effect of both cytokines on the activities of nuclear factor kappa B (NF-kappa B) and nuclear IL-6 NL-IL 6), transcription factors that are essential for IL-6 gene expression.
We evaluated IL-6 synthesis, mRNA expression, and mRNA stability by ELISA, Northern analysis, and the actinomycin D method, respectively. Activities of NF-kappa B and NF-IL 6 were analyzed by gel shift assay.
IL-4 augmented the IL-1 stimulated IL-6 mRNA levels by about threefold without altering mRNA stability. IL-1 treatment rapidly induced the binding activity of NF-kappa B. In contrast, IL-4 did not affect basal and IL-1-induced NF-kappa B activities. Both IL-1 and IL-4 stimulated NF-IL6 activity as early as 30 minutes after treatment. When MC were treated with both cytokines together, marked activation of NF-IL6 was observed at five hours.
These results suggest that simultaneous activation of NF-kappa B and NF-IL6 is essential for IL-6 gene expression and that IL-1 and IL-4 cooperatively stimulate MC IL-6 production through their synergistic activation of NF-IL6.
虽然白细胞介素（IL）-4可抑制人单核细胞促炎细胞因子的表达，但我们观察到它可增强IL-1激活的人系膜细胞（MC）产生IL-6的能力。为研究MC中IL-1与IL-4这种细胞类型特异性相互作用的机制，我们检测了这两种细胞因子对核因子κB（NF-κB）和核IL-6（NF-IL6）活性的影响，这两种转录因子对IL-6基因表达至关重要。
我们分别通过酶联免疫吸附测定法（ELISA）、Northern印迹分析和放线菌素D法评估IL-6的合成、mRNA表达及mRNA稳定性。通过凝胶迁移试验分析NF-κB和NF-IL6的活性。
IL-4使IL-1刺激的IL-6 mRNA水平增加约三倍，而不改变mRNA稳定性。IL-1处理可迅速诱导NF-κB的结合活性。相比之下，IL-4不影响基础状态及IL-1诱导的NF-κB活性。IL-1和IL-4在处理后30分钟即可刺激NF-IL6活性。当MC同时用这两种细胞因子处理时，在5小时时观察到NF-IL6明显激活。
这些结果表明，NF-κB和NF-IL6的同时激活对IL-6基因表达至关重要，且IL-1和IL-4通过协同激活NF-IL6来协同刺激MC产生IL-6。
