SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation in mouse macrophage Raw264.7 cells.
SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation in mouse macrophage Raw264.7 cells.
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DOI：
10.3892/mmr.2017.6492
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发表时间：
2017-06
影响因子：
3.4
通讯作者：
Chosa N
中科院分区：
文献类型：
--
作者：
Inoue M;Yamada J;Aomatsu-Kikuchi E;Satoh K;Kondo H;Ishisaki A;Chosa N
最近，我们确定了间充质干细胞（MSC）分泌的羊瘙痒症反应基因1（SCRG 1）及其受体骨髓基质细胞抗原1（BST 1）作为干细胞质量，如自我更新，迁移能力，和成骨分化潜力的正调控因子。在这里，我们研究了SCRG 1在巨噬细胞中的旁分泌活性的影响。小鼠巨噬细胞样细胞系Raw 264.7表达BST 1/β1或BST 1/β2整合素作为可能的SCRG 1受体。出乎意料的是，重组SCRG 1没有增强这些巨噬细胞中的细胞增殖、迁移或粘附。然而，进一步检查SCRG 1在Raw 264.7细胞中的作用确实揭示了有效的抗炎作用，其中SCRG 1抑制LPS诱导的CCL 22产生。SCRG 1还诱导这些细胞中细胞外信号调节激酶1/2（ERK 1/2）的磷酸化，此外，丝裂原活化蛋白激酶（MAPK）/ERK激酶抑制剂U 0126显著抑制SCRG 1对LPS诱导的趋化因子CCL 22产生的作用。综上所述，这些数据表明，SCRG 1通过MAPK途径进行信号传导并抑制LPS信号传导途径。众所周知，CCL 22对单核细胞、树突状细胞、自然杀伤细胞和慢性活化的T淋巴细胞具有趋化性，这表明MSC衍生的SCRG 1可以阻断这些细胞的浸润。提出了MSC通过抑制单核细胞/巨噬细胞谱系细胞中的趋化因子表达而发挥其免疫抑制作用的机制。
Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1 (BST1) as positive regulators of stem cell qualities such as self-renewal, migration abilities, and osteogenic differentiation potential. Here, we examined the effect of the paracrine activity of SCRG1 in macrophages. The mouse macrophage-like cell line Raw264.7 expressed BST1/β1 or BST1/β2 integrin as possible SCRG1 receptors. Unexpectedly, recombinant SCRG1 did not enhance cell proliferation, migration, or adhesion in these macrophages. However, further examination of the effect of SCRG1 in Raw264.7 cells did reveal a potent anti-inflammatory effect whereby SCRG1 suppressed LPS-induced CCL22 production. SCRG1 also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in these cells and, moreover, a mitogen-activated protein kinase (MAPK)/ERK kinase inhibitor U0126 significantly suppressed the effect of SCRG1 on LPS-induced chemokine CCL22 production. Taken together, these data indicate that SCRG1 signals through the MAPK pathway and suppresses the LPS signaling pathway. CCL22 is generally known to be chemotactic for monocytes, dendritic cells, natural killer cells and chronically activated T lymphocytes, suggesting that MSC-derived SCRG1 may block infiltration of these cells. A mechanism is proposed by which MSCs play their immunosuppressive role through suppressing chemokine expression in monocyte/macrophage lineage cells.