Caldecrin inhibits lipopolysaccharide-induced pro-inflammatory cytokines and M1 macrophage polarization through the immunoreceptor triggering receptor expressed in myeloid cells-2
Caldecrin inhibits lipopolysaccharide-induced pro-inflammatory cytokines and M1 macrophage polarization through the immunoreceptor triggering receptor expressed in myeloid cells-2
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DOI：
10.1016/j.bbrc.2020.01.045
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发表时间：
2020-03-19
影响因子：
3.1
通讯作者：
Tomomura, Akito
中科院分区：
文献类型：
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作者：
Bandow, Kenjiro;Hasegawa, Hiroya;Tomomura, Akito
Caldecrin是从胰腺中分离出来的一种血清降钙因子，可抑制核因子-kappa B受体激活剂(RANKL)诱导的破骨细胞钙振荡通路。在此，我们探讨了钙蛋白对巨噬细胞内毒素-Toll样受体-4(TLR-4)信号通路的影响。Caldecrin抑制脂多糖诱导的小鼠骨髓巨噬细胞和RAW264.7小鼠巨噬细胞系的促炎细胞因子基因表达和M1巨噬细胞极化。接下来，我们重点研究了RANKL受体和TLR-4共同的共同受体TREM2-2(TREM-2)的触发作用，并建立了TREM2-KO RAW264.7细胞，其中TREM2基因用CRISPR/Cas9系统进行了缺失。在TREM2-KO RAW264.7细胞中，未观察到Caldecrin介导的促炎细胞因子表达和M1巨噬细胞极化的改变。这些结果表明，钙化蛋白不仅是破骨细胞激活的抑制因子，也是脂多糖诱导的炎症反应的负调节因子，通过TREM-2发挥作用。(C)2020 Elsevier Inc.保留所有权利。
Caldecrin was previously isolated as a serum calcium-decreasing factor from the pancreas and is known to suppress receptor activator of nuclear factor-kappa B ligand (RANKL)-induced calcium oscillation pathways in osteoclasts. Here, we explored the effects of caldecrin on lipopolysaccharide (LPS)-Toll-like receptor-4 (TLR-4) signaling pathways in macrophages. Caldecrin inhibited the LPS-induced gene expression of proinflammatory cytokines and M1 macrophage polarization in mouse bone marrow macrophages and the RAW264.7 mouse macrophage cell line. Next, we focused on triggering receptor expressed in myeloid cells-2 (TREM-2) as a co-receptor common to RANKL receptor and TLR-4, and established Trem2-KO RAW264.7 cells, in which Trem2 gene was deleted using the CRISPR/Cas9 system. Caldecrin-mediated alterations in pro-inflammatory cytokine expression and M1 macrophage polarization were not observed in Trem2-KO RAW264.7 cells. These results suggest that caldecrin is not only an inhibitor of osteoclast activation but also a negative regulator of LPS-induced inflammatory responses, functioning via TREM-2. (C) 2020 Elsevier Inc. All rights reserved.