Chloroquine and Rapamycin Augment Interleukin-37 Expression via the LC3, ERK, and AP-1 Axis in the Presence of Lipopolysaccharides
Chloroquine and Rapamycin Augment Interleukin-37 Expression via the LC3, ERK, and AP-1 Axis in the Presence of Lipopolysaccharides
复制标题
在存在脂多糖的情况下，氯喹和雷帕霉素通过 LC3、ERK 和 AP-1 轴增强白细胞介素 37 的表达
DOI：
10.1155/2020/6457879
复制
发表时间：
2020-02
影响因子：
4.1
通讯作者：
陈颂（Song Chen）
中科院分区：
文献类型：
--
作者：
师晓毅（Xiaoyi Shi）;陈颂（Song Chen）
IL-37是一种细胞因子，在许多代谢性炎性疾病中起关键的保护作用，其治疗潜力已通过外源性IL-37给药得到证实。然而，其监管机制仍不清楚。在有或没有LPS刺激的情况下，用自噬修饰试剂（3-MA、氯喹和雷帕霉素）处理U937细胞。此后，测定IL-37表达和自噬标志物（Beclin 1、P62/SQSTM 1和LC 3）。对于调节信号通路，对NF-κB（p65和IκBα）、AP-1（c-Fos/c-Jun）和MAPK信号通路（Erk 1/2和p38 MAPK）的磷酸化蛋白进行定量，并且还使用MAPK和NF-κB通路的激动剂和拮抗剂。健康人外周血单核细胞进行类似的处理，以确认我们的结果。四只恒河猴也给予氯喹，以评价IL-37在体内的诱导作用及其对CD 4增殖和活化的生物活性。在LPS存在下，U937细胞和人PBMC中的IL-37被雷帕霉素和氯喹上调。IL-37在与LC 3转化相关的自噬细胞中优先诱导。AP-1和p65结合基序可以在IL-37启动子的序列中推断。诱导性IL-37表达伴随着磷酸化Erk 1/2和AP-1的增加，并且可以被Erk 1/2抑制剂完全消除或被Erk 1/2激动剂增强。在猴子中，氯喹增加了IL-37的表达，这与CD 4增殖和磷酸化STAT 3呈负相关。雷帕霉素和氯喹通过LC 3、Erk 1/2和NF-κB/AP-1途径诱导IL-37水平。也可以在体内诱导功能性IL-37。
IL-37 is a cytokine that plays critical protective roles in many metabolic inflammatory diseases, and its therapeutic potential has been confirmed by exogenous IL-37 administration. However, its regulatory mechanisms remain unclear. U937 cells were treated with autophagy-modifying reagents (3-MA, chloroquine, and rapamycin) with or without LPS stimulation. Thereafter, IL-37 expression and autophagic markers (Beclin1, P62/SQSTM1, and LC3) were determined. For regulatory signal pathways, phosphorylated proteins of NF-κB (p65 and IκBα), AP-1 (c-Fos/c-Jun), and MAPK signal pathways (Erk1/2 and p38 MAPK) were quantified, and the agonists and antagonists of MAPK and NF-κB pathways were also used. Healthy human peripheral blood mononuclear cells were treated similarly to confirm our results. Four rhesus monkeys were also administered chloroquine to evaluate IL-37 induction in vivo and its bioactivity on CD4 proliferation and activation. IL-37 was upregulated by rapamycin and chloroquine in both U937 cells and human PBMCs in the presence of LPS. IL-37 was preferentially induced in autophagic cells associated with LC3 conversion. AP-1 and p65 binding motifs could be deduced in the sequence of the IL-37 promoter. Inductive IL-37 expression was accompanied with increased phosphorylated Erk1/2 and AP-1 and could be completely abolished by an Erk1/2 inhibitor or augmented by Erk1/2 agonists. In monkeys, chloroquine increased IL-37 expression, which was inversely correlated with CD4 proliferation and phosphorylated STAT3. IL-37 levels were induced by rapamycin and chloroquine through the LC3, Erk1/2, and NF-κB/AP-1 pathways. Functional IL-37 could also be induced in vivo.
登录
查看更多内容
影响因子：
5.5
作者：
Rudloff, Ina;Cho, Steven X.;Nold, Marcel F.
通讯作者：
Nold, Marcel F.
DOI：
10.1038/nri.2016.100
发表时间：
2016-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Cadwell K
通讯作者：
Cadwell K
影响因子：
4.8
作者：
Kumar, S;McDonnell, PC;Young, PR
通讯作者：
Young, PR
DOI：
10.1152/ajprenal.00461.2007
发表时间：
2008-05-01
影响因子：
4.2
作者：
Yasuda, Hideo;Leelahavanichkul, Asada;Star, Robert A.
通讯作者：
Star, Robert A.
影响因子：
7.3
作者：
van de Veerdonk FL;Netea MG
通讯作者：
Netea MG