TGF-β1 Stimulates Mouse Macrophages to Express APRIL through Smad and p38MAPK/CREB Pathways
TGF-β1 Stimulates Mouse Macrophages to Express APRIL through Smad and p38MAPK/CREB Pathways
复制标题
DOI：
10.1007/s10059-011-1040-4
复制
发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Kim, Pyeung-Hyeun
中科院分区：
文献类型：
--
作者：
Jang, Young-Saeng;Kim, Jae-Hee;Kim, Pyeung-Hyeun
增殖诱导配体 (APRIL) 是 TNF 家族的新成员，支持 B 细胞存活和肿瘤细胞增殖。 APRIL 由巨噬细胞、树突状细胞和活化的 T 细胞分泌为可溶性蛋白。然而，参与 APRIL 表达调节的因素尚不清楚。在这项研究中，我们研究了 TGF-β1 对小鼠巨噬细胞系 P388D1 中 APRIL 表达的影响。 TGF-β1 以时间和剂量依赖性方式诱导 APRIL mRNA 表达。每毫升 1 纳克的 TGF-β1 是最佳浓度，APRIL 转录物最早在刺激后 3 小时就出现。根据我们的研究，包括 Smad3、DN-Smad3 和 sh-Smad3 的过度表达，我们发现 Smad3 至少部分介导 APRIL 转录。此外，使用抑制剂的实验表明，p38MAPK 和 CREB 也参与 TGF-β1 诱导的 APRIL 表达。这些结果表明TGF-β1通过Smad3和p38MAPK/CREB信号通路刺激巨噬细胞中的APRIL表达。
A proliferation-inducing ligand (APRIL), a new TNF family member, supports B-cell survival and tumor cell proliferation. APRIL is secreted as a soluble protein by macrophages, dendritic cells and activated T cells. However, factors involved in regulation of APRIL expression are as yet unknown. In this study, we investigated the effect of TGF-beta 1 on APRIL expression in P388D1, a mouse macrophage cell line. TGF-beta 1 induced APRIL mRNA expression in a time-and dose-dependent manner. One nanogram per milliliter of TGF-beta 1 was optimal and APRIL transcripts appeared as early as 3 h after stimulation. Based on our studies, which included overexpression of Smad3, DN-Smad3, and sh-Smad3, we found that Smad3 mediates APRIL transcription at least partially. Further, experiments using inhibitors revealed that p38MAPK and CREB are also involved in TGF-beta 1-induced APRIL expression. These results suggest that TGF-beta 1, through Smad3 and p38MAPK/CREB signaling pathways, stimulates APRIL expression in macrophages.