Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway
Objectives: Macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) play an important role in the occurrence and progression of atherosclerosis. Fatty acid–binding protein 4 (FABP4), mainly existing in macrophages and adipocytes, can influence lipid metabolism and inflammation regulated...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:0fb6b2e5e1a244cdabccac43a8b63c912021-12-01T23:08:33ZIntermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway1663-981210.3389/fphar.2021.724777https://doaj.org/article/0fb6b2e5e1a244cdabccac43a8b63c912021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.724777/fullhttps://doaj.org/toc/1663-9812Objectives: Macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) play an important role in the occurrence and progression of atherosclerosis. Fatty acid–binding protein 4 (FABP4), mainly existing in macrophages and adipocytes, can influence lipid metabolism and inflammation regulated by macrophages. Herein, we first established the connection between intermedin (IMD: a new peptide that has versatile biological activities in the cardiovascular system) and FABP4 and then investigated the influence of IMD on ox-LDL-induced changes in RAW264.7 macrophages line.Methods: The bioinformatics analysis, such as gene ontology enrichment and protein–protein interactions, was performed. For ox-LDL–stimulated assays, RAW264.7 was first pretreated with IMD and then exposed to ox-LDL. To explore the cell signaling pathways of IMD on inflammatory inhibition, main signaling molecules were tested and then cells were co-incubated with relevant inhibitors, and then exposed/not exposed to IMD. Finally, cells were treated with ox-LDL. The protein and gene expression of FABP4, IL-6, and TNF-α were quantified by WB/ELISA and RT-qPCR.Results: In the ox-LDL-stimulated assays, exposure of the RAW264.7 macrophages line to ox-LDL reduced cell viability and increased the expression of FABP4, as well as induced the release of IL-6 and TNF-α (all p < 0.05). On the other hand, IMD prevented ox-LDL–induced cell toxicity, FABP4 expression, and the inflammatory level in RAW264.7 (all p < 0.05) in a dose-dependent manner. The inhibition of FABP4 and the anti-inflammatory effect of IMD were partially suppressed by the protein kinase A (PKA) inhibitor H-89.Conclusion: IMD can prevent ox-LDL–induced macrophage inflammation by inhibiting FABP4, whose signaling might partially occur via the PKA pathway.Kai LiuRufeng ShiRufeng ShiSi WangQi LiuHengyu ZhangXiaoping ChenFrontiers Media S.A.articleintermedin (17-47)/adrenomedullin 2 (17-47)fatty acid–binding protein 4inflammationRAW264.7 cellsPKATherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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EN |
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intermedin (17-47)/adrenomedullin 2 (17-47) fatty acid–binding protein 4 inflammation RAW264.7 cells PKA Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
intermedin (17-47)/adrenomedullin 2 (17-47) fatty acid–binding protein 4 inflammation RAW264.7 cells PKA Therapeutics. Pharmacology RM1-950 Kai Liu Rufeng Shi Rufeng Shi Si Wang Qi Liu Hengyu Zhang Xiaoping Chen Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway |
| description |
Objectives: Macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) play an important role in the occurrence and progression of atherosclerosis. Fatty acid–binding protein 4 (FABP4), mainly existing in macrophages and adipocytes, can influence lipid metabolism and inflammation regulated by macrophages. Herein, we first established the connection between intermedin (IMD: a new peptide that has versatile biological activities in the cardiovascular system) and FABP4 and then investigated the influence of IMD on ox-LDL-induced changes in RAW264.7 macrophages line.Methods: The bioinformatics analysis, such as gene ontology enrichment and protein–protein interactions, was performed. For ox-LDL–stimulated assays, RAW264.7 was first pretreated with IMD and then exposed to ox-LDL. To explore the cell signaling pathways of IMD on inflammatory inhibition, main signaling molecules were tested and then cells were co-incubated with relevant inhibitors, and then exposed/not exposed to IMD. Finally, cells were treated with ox-LDL. The protein and gene expression of FABP4, IL-6, and TNF-α were quantified by WB/ELISA and RT-qPCR.Results: In the ox-LDL-stimulated assays, exposure of the RAW264.7 macrophages line to ox-LDL reduced cell viability and increased the expression of FABP4, as well as induced the release of IL-6 and TNF-α (all p < 0.05). On the other hand, IMD prevented ox-LDL–induced cell toxicity, FABP4 expression, and the inflammatory level in RAW264.7 (all p < 0.05) in a dose-dependent manner. The inhibition of FABP4 and the anti-inflammatory effect of IMD were partially suppressed by the protein kinase A (PKA) inhibitor H-89.Conclusion: IMD can prevent ox-LDL–induced macrophage inflammation by inhibiting FABP4, whose signaling might partially occur via the PKA pathway. |
| format |
article |
| author |
Kai Liu Rufeng Shi Rufeng Shi Si Wang Qi Liu Hengyu Zhang Xiaoping Chen |
| author_facet |
Kai Liu Rufeng Shi Rufeng Shi Si Wang Qi Liu Hengyu Zhang Xiaoping Chen |
| author_sort |
Kai Liu |
| title |
Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway |
| title_short |
Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway |
| title_full |
Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway |
| title_fullStr |
Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway |
| title_full_unstemmed |
Intermedin Inhibits the Ox-LDL–Induced Inflammation in RAW264.7 Cells by Affecting Fatty Acid–Binding Protein 4 Through the PKA Pathway |
| title_sort |
intermedin inhibits the ox-ldl–induced inflammation in raw264.7 cells by affecting fatty acid–binding protein 4 through the pka pathway |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/0fb6b2e5e1a244cdabccac43a8b63c91 |
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