Resveratrol downregulates TNF-α-induced monocyte chemoattractant protein-1 in primary rat pulmonary artery endothelial cells by P38 mitogen-activated protein kinase signaling
Authors Lin JW, Yang LH, Ren ZC, Mu DG, Li YQ, Yan JP, Wang LX, Chen C
Received 21 August 2018
Accepted for publication 4 March 2019
Published 27 May 2019 Volume 2019:13 Pages 1843—1853
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Arun Kapoor
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Cristiana Tanase
Jian-Wei Lin,1 Le-He Yang,2 Zhuo-Chao Ren,3 De-Guang Mu,3 Ya-Qing Li,3 Jian-Ping Yan,3 Liang-Xing Wang,4 Chun Chen3
1Department of Cardiology, Xiasha Campus, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310018, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, Wenzhou Medical University, Wenzhou 325600, Zhejiang, People’s Republic of China; 3Department of Respiratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, People’s Republic of China; 4Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China
Background: To evaluate the effects of resveratrol to monocyte chemoattractant protein-1 (MCP-1) and the role of p38 mitogen-activated protein kinase (MAPK) in this process in vitro.
Materials and methods: Animal acute pulmonarythromboembolism (PTE) model: rat model was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. One hundred and thirty-two rats were randomly and equally divided into ten groups: rats-control (untreated), rats-1% DMSO, rats-TNF-α, rats-TNF-α + resveratrol, rats-TNF-α +C1142, rats-TNF-α+SB203580, rats-TNF-α+resveratrol + SB203580, rats-resveratrol only, rats-C1142 only, and rats-SB203580 only. Rat pulmonary artery endothelial cells (RPAs) tests: RPAs were isolated from above animal and designated as: RPAs-control, RPAs-1% DMSO control, RPAs-TNF-α, RPAs-TNF-α + resveratrol, RPAs-TNF-α + C1142, RPAs-TNF-α + SB203580, RPAs-TNF-α + resveratrol + SB203580, RPAs-resveratrol only, RPAs-C1142 only, and RPAs-SB203580 only. Each group was further divided into 1, 4, and 8 hrs time point for evaluation (n=6 rats per time point) except RPAs-TNF-α + SB203580, RPAs-TNF-α + resveratrol + SB203580, RPAs-C1142 and RPAs-SB203580 only, which were evaluated at 8 hrs time point. At each time point, mRNA and protein expressions of RPAs of MCP-1 were measured. The phosphorylation of p38 MAPK (p-pMAPK) of RPAs was also detected.
Results: We found that the RPAs-TNF-α elicited significant increases in MCP-1 expression and phosphorylation of p38 mitogen-activated protein kinase (p-p38 MAPK). Furthermore, the MCP-1 expressions of RPAs-Resveratrol, RPAs-C1142, and RPAs-SB203580 were significantly down-regulated, which was associated with robustly suppressed TNF-α-induced p-p38MAPK expression.
Conclusion: Our findings suggested that MCP-1 was involved in the formation of TNF-α-induced inflammatory response, and resveratrol could down-regulate the expression of MCP-1 via TNF-α- inhibition, which might contribute to the decline of acute PTE-induced PH in vivo.
Keywords: inflammation, pulmonary artery endothelial cells, pulmonary hypertension, pulmonary thromboembolism, resveratrol
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]