Fuqua C F, Akomeah R, Price J O, Adunyah S E
Department of Cancer Biology, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN 37208, USA.
Cytokine. 2008 Oct;44(1):101-7. doi: 10.1016/j.cyto.2008.06.010. Epub 2008 Aug 15.
Cytokines play an important role in the immune system, and abnormalities in their production have been found in many human diseases. Interleukin-21 (IL-21), a type I cytokine produced by activated T cells, has diverse effects on the immune system, but its ability to induce production of other cytokines is not well delineated. Furthermore, the signaling pathway underlying its action is poorly understood. Here, we have evaluated IL-21-induced cytokine production in human monocytes and U937 leukemia cells. We found that IL-21 induces upregulation of a variety of cytokines from multiple cytokine families. We also found that IL-21 triggers rapid activation of ERK1/2. Neutralizing antibody to the IL-21R prevented both IL-21-induced cytokine production and IL-21-induced activation of ERK1/2. Inhibition of ERK1/2 activity by the ERK-selective inhibitor U0126 reverses the ability of IL-21 to upregulate cytokine production, suggesting that IL-21-induced cytokine production is dependent on ERK1/2 activation.
细胞因子在免疫系统中发挥着重要作用，并且在许多人类疾病中都发现了其产生异常。白细胞介素-21（IL-21）是一种由活化T细胞产生的I型细胞因子，对免疫系统具有多种作用，但其诱导其他细胞因子产生的能力尚未得到充分阐明。此外，其作用的信号通路也知之甚少。在此，我们评估了IL-21在人单核细胞和U937白血病细胞中诱导细胞因子产生的情况。我们发现IL-21可诱导多种细胞因子家族的多种细胞因子上调。我们还发现IL-21可触发ERK1/2的快速激活。针对IL-21R的中和抗体可阻止IL-21诱导的细胞因子产生以及IL-21诱导的ERK1/2激活。ERK选择性抑制剂U0126对ERK1/2活性的抑制可逆转IL-21上调细胞因子产生的能力，这表明IL-21诱导的细胞因子产生依赖于ERK1/2激活。
