Glucagon-Like Peptide-1 Receptor Regulates Macrophage Migration in Monosodium Urate-Induced Peritoneal Inflammation.
Glucagon-Like Peptide-1 Receptor Regulates Macrophage Migration in Monosodium Urate-Induced Peritoneal Inflammation.
复制标题
胰高血糖素样肽-1 受体调节尿酸钠诱导的腹膜炎症中巨噬细胞的迁移
DOI：
10.3389/fimmu.2022.772446
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发表时间：
2022
影响因子：
7.3
通讯作者：
Zhong J
中科院分区：
文献类型：
--
作者：
Chen J;Mei A;Liu X;Braunstein Z;Wei Y;Wang B;Duan L;Rao X;Rajagopalan S;Dong L;Zhong J
胰高血糖素样肽-1（GLP-1）是一种促胰岛素肽，通过GLP-1受体（GLP-1 R）发出信号。因此，GLP-1 R在糖尿病和心血管疾病中起着关键作用。GLP-1 R是否参与痛风等炎症性疾病仍不清楚。巨噬细胞是痛风发病机制中的关键效应细胞，痛风是由关节中尿酸沉积引起的常见形式的炎性关节炎。由于现有抗GLP-1 R抗体缺乏特异性，因此GLP-1 R在蛋白水平的表达存在争议。利用GLP-1 R启动子调控下表达增强型绿色荧光蛋白（EGFP）的转基因小鼠模型，证实巨噬细胞表达GLP-1 R。M2型巨噬细胞和Ly 6C+巨噬细胞表达的GLP-1 R水平高于其对应物。GLP-1 R缺陷型巨噬细胞的迁移能力降低，白细胞介素（IL）-6的表达增强，而IL-1β的表达不受影响。在尿酸盐（MSU）晶体诱导的腹膜炎（一种痛风实验模型）中，与野生型小鼠相比，GLP-1 R敲除小鼠中巨噬细胞（尤其是M2巨噬细胞）的募集受到显著抑制。总之，我们的数据表明，GLP-1 R在MSU诱导的炎症中的巨噬细胞迁移中起关键作用。
Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide that signals through the GLP-1 receptor (GLP-1R). GLP-1R, therefore, plays a critical role in diabetes and cardiovascular disease. Whether GLP-1R is involved in inflammatory disease such as gout remains unclear. Macrophages are critical effector cells in the pathogenesis of gout, a common form of inflammatory arthritis caused by the deposition of uric acid in joints. The expression of GLP-1R at the protein level is controversial due to the lack of specificity of existing antibodies against GLP-1R. Using a transgenic mouse model expressing enhanced green fluorescent protein (EGFP) under the control of GLP-1R promoter, here we confirmed the expression of GLP-1R by macrophages. M2 type macrophages and Ly6C+ macrophages expressed higher levels of GLP-1R, compared to their counterparts. GLP-1R deficient macrophages displayed a reduced the migratory ability and an enhanced expression of interleukin (IL)-6, while the expression of IL-1β was not affected. In monosodium urate (MSU) crystal-induced peritonitis, an experimental model of gout, the recruitment of macrophages, especially M2 macrophages, was significantly suppressed in GLP-1R knockout mice compared to wild-type mice. In conclusion, our data suggests that GLP-1R plays a critical role in macrophage migration in MSU-induced inflammation.