GLP-1 受体激动剂通过激活 AMPK 来抑制角质形成细胞的炎症信号。
GLP-1 receptor agonist impairs keratinocytes inflammatory signals by activating AMPK.
机构信息
Department of Dermatology and Venerology，Chongqing Three Gorges Central Hospital, ChongQing 404100, China.
Department of Dermatology and Venerology，Chongqing Three Gorges Central Hospital, ChongQing 404100, China.
出版信息
Exp Mol Pathol. 2019 Apr;107:124-128. doi: 10.1016/j.yexmp.2019.01.014. Epub 2019 Feb 15.
PURPOSE
Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, is an antidiabetic drug. It has been shown to improve the Psoriasis Area and Severity Index (PASI) in patients with type 2 diabetes and psoriasis in clinical practice, but the mechanism remains somewhat unclear. We used lipopolysaccharides (LPS) to induce inflammatory response in keratinocytes and explore the mechanism.
METHODS
The HaCat cells were incubated with LPS for 16 h and then were treated with liraglutide for 30 min. Cell viability was testing by CCK-8 assay. GLP-1Rs and intracellular signaling pathways were identified by Western blot. The migration of macrophage was detecting by trans-well assay.
RESULTS
Liraglutide decreased cell viability in the HaCat cells. Liraglutide restrained the migration of macrophage to the HaCat cells. LPS elevated not only the protein abundance of phospho-IKKα/β S176/S180, phospho-NF-κB p65, phospho-JAK2, phospho-STAT3 and SOCS3, but also the levels of TNF-α and IL-6 in the HaCat cells. These effects of LPS were reversed by liraglutide. In addition, liraglutide increased phosphorylation of AMPK. The AMPK inhibitor Compound (CC) impaired liraglutide-inhibited p-NF-κB p65 and p-STAT3.
CONCLUSIONS
GLP-1 impaired keratinocytes inflammatory signals by activating AMPK and restrained macrophage migration.
目的
利拉鲁肽是一种胰高血糖素样肽-1（GLP-1）类似物，是一种抗糖尿病药物。在临床实践中，它已被证明可以改善 2 型糖尿病和银屑病患者的银屑病面积和严重程度指数（PASI），但其机制仍有些不清楚。我们使用脂多糖（LPS）诱导角质形成细胞中的炎症反应，并探讨其机制。
方法
将 HaCat 细胞与 LPS 孵育 16 小时，然后用利拉鲁肽处理 30 分钟。通过 CCK-8 测定法检测细胞活力。通过 Western blot 鉴定 GLP-1R 和细胞内信号通路。通过 Trans-well 测定法检测巨噬细胞的迁移。
结果
利拉鲁肽降低了 HaCat 细胞中的细胞活力。利拉鲁肽抑制了巨噬细胞向 HaCat 细胞的迁移。LPS 不仅增加了 HaCat 细胞中磷酸化 IKKα/β S176/S180、磷酸化 NF-κB p65、磷酸化 JAK2、磷酸化 STAT3 和 SOCS3 的蛋白丰度，还增加了 TNF-α 和 IL-6 的水平。利拉鲁肽逆转了 LPS 的这些作用。此外，利拉鲁肽增加了 AMPK 的磷酸化。AMPK 抑制剂 Compound (CC) 削弱了利拉鲁肽抑制的 p-NF-κB p65 和 p-STAT3。
结论
GLP-1 通过激活 AMPK 损害角质形成细胞的炎症信号，并抑制巨噬细胞迁移。
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