自噬通过下调内皮细胞中p38丝裂原活化蛋白激酶/雷帕霉素靶蛋白信号级联反应来抑制炎症。

Autophagy Inhibits Inflammation via Down-Regulation of p38 MAPK/mTOR Signaling Cascade in Endothelial Cells.

作者信息

Zhou Ling, Wang Juanjuan, Hou Hui, Li Jiao, Li Juan, Liang Jiannan, Li Junqin, Niu Xuping, Hou Ruixia, Zhang Kaiming

机构信息

Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.

Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, People's Republic of China.

出版信息

Clin Cosmet Investig Dermatol. 2023 Mar 14;16:659-669. doi: 10.2147/CCID.S405068. eCollection 2023.

DOI:10.2147/CCID.S405068

PMID:36942318

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10024493/

Abstract

OBJECTIVE

Autophagy, an intracellular process of self-digestion, has been shown to modulate inflammatory responses. In the present study, we determined the effects of autophagy on inflammatory response induced by M5 cytokines.

METHODS

Human umbilical vein endothelial cells (HUVECs) were treated with M5 cytokines to induce inflammation. Expression levels of mRNA for inflammatory cytokines and BIRC2 were compared in HUVECs with vs without induction of autophagy with rapamycin (RAPA) by PCR, while cell apoptosis was assessed by flow cytometry and caspase-3 activity assay kit. Expression levels of LC3, p62, p-p38 MAPK (Thr180/Tyr182), p-mTOR (Ser2445) and p-ULK1 (Ser555) proteins were measured by Western blotting. The nitric oxide (NO) content, NO synthase (NOS) activity and cell angiogenesis were also evaluated.

RESULTS

Induction of autophagy with RAPA decreased expression levels of IL6, IL8 and CCL20, in addition to reduction in inflammation-induced apoptosis in HUVECs. Moreover, RAPA increased LC3II, while decreasing p62 expression. Likewise, expression levels of p-p38 MAPK and p-mTOR proteins were markedly decreased by the treatment with RAPA. Finally, RAPA treatment increased the NO content and the NOS activity, and inhibited angiogenesis.

CONCLUSION

Induced autophagy can improve the function of endothelial cells in psoriasis, suggesting approaches to induce autophagy can be used to ameliorate psoriasis.

摘要

目的

自噬是一种细胞内自我消化过程，已被证明可调节炎症反应。在本研究中，我们确定了自噬对M5细胞因子诱导的炎症反应的影响。

方法

用人脐静脉内皮细胞（HUVECs）与M5细胞因子共同处理以诱导炎症。通过PCR比较用雷帕霉素（RAPA）诱导自噬和未诱导自噬的HUVECs中炎性细胞因子和BIRC2的mRNA表达水平，同时通过流式细胞术和caspase-3活性检测试剂盒评估细胞凋亡。通过蛋白质印迹法检测LC3、p62、p-p38 MAPK（Thr180/Tyr182）、p-mTOR（Ser2445）和p-ULK1（Ser555）蛋白的表达水平。还评估了一氧化氮（NO）含量、一氧化氮合酶（NOS）活性和细胞血管生成。

结果

用RAPA诱导自噬除了降低HUVECs中炎症诱导的细胞凋亡外，还降低了IL6、IL8和CCL20的表达水平。此外，RAPA增加了LC3II，同时降低了p62表达。同样，用RAPA处理后p-p38 MAPK和p-mTOR蛋白的表达水平明显降低。最后，RAPA处理增加了NO含量和NOS活性，并抑制了血管生成。