Ismail Hassan Ahmed Hassan Ahmed, Kang Byung-Hun, Kim Jae-Su, Lee Jae-Hyung, Choi In-Wook, Cha Guang-Ho, Yuk Jae-Min, Lee Young-Ha
Department of Infection Biology, Chungnam National University School of Medicine, Daejeon 34134, Korea.
Department of Obstetrics and Gynecology, Chungnam National University School of Medicine, Daejeon 34134, Korea.
Korean J Parasitol. 2017 Dec;55(6):613-622. doi: 10.3347/kjp.2017.55.6.613. Epub 2017 Dec 31.
IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.
白细胞介素-12(IL-12)和白细胞介素-23(IL-23)在结构上密切相关,并且已被证明在免疫反应调节中发挥关键作用。然而,关于这些细胞因子在T细胞中的调节机制知之甚少。在此,我们研究了磷脂酰肌醇-3激酶(PI3K)和丝裂原活化蛋白激酶(MAPK)信号通路在人Jurkat T细胞响应刚地弓形虫和脂多糖(LPS)时产生IL-12和IL-23过程中的作用。用刚地弓形虫或LPS刺激后,T细胞中IL-12和IL-23的产生显著增加。刚地弓形虫和LPS刺激后10分钟,T细胞中AKT、细胞外信号调节激酶1/2(ERK1/2)、p38 MAPK和应激活化蛋白激酶1/2(JNK1/2)的磷酸化水平升高,并在30 - 60分钟达到峰值。抑制PI3K信号通路可降低刚地弓形虫感染细胞中IL-12和IL-23的产生,但在LPS刺激的细胞中则增加。ERK1/2和p38 MAPK抑制剂可显著降低刚地弓形虫和LPS刺激细胞中IL-12和IL-23的产生,但JNK1/2抑制剂处理的细胞中则无此现象。总体而言,在刚地弓形虫感染的Jurkat细胞中,PI3K和JNK1/2对IL-12和IL-23的产生起正调节作用,而在LPS刺激的细胞中起负调节作用。ERK1/2和p38 MAPK对Jurkat T细胞中IL-12和IL-23的产生起正调节作用。这些数据表明,刚地弓形虫和LPS通过调节PI3K和MAPK信号通路诱导Jurkat T细胞产生IL-12和IL-23;然而,刚地弓形虫刺激Jurkat T细胞产生IL-12和IL-23的潜在机制与LPS不同。