PMID- 31213772 OWN - NLM STAT- MEDLINE DCOM- 20191223 LR - 20200225 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 13 DP - 2019 TI - Resveratrol downregulates TNF-alpha-induced monocyte chemoattractant protein-1 in primary rat pulmonary artery endothelial cells by P38 mitogen-activated protein kinase signaling. PG - 1843-1853 LID - 10.2147/DDDT.S184785 [doi] AB - 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 pulmonary thromboembolism (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-alpha, rats-TNF-alpha + resveratrol, rats-TNF-alpha +C1142, rats-TNF-alpha+SB203580, rats-TNF-alpha+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-alpha, RPAs-TNF-alpha + resveratrol, RPAs-TNF-alpha + C1142, RPAs-TNF-alpha + SB203580, RPAs-TNF-alpha + 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-alpha + SB203580, RPAs-TNF-alpha + 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-alpha 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-alpha-induced p-p38MAPK expression. Conclusion: Our findings suggested that MCP-1 was involved in the formation of TNF-alpha-induced inflammatory response, and resveratrol could down-regulate the expression of MCP-1 via TNF-alpha- inhibition, which might contribute to the decline of acute PTE-induced PH in vivo. FAU - Lin, Jian-Wei AU - Lin JW AD - Department of Cardiology, Xiasha Campus, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310018, Zhejiang, People's Republic of China. FAU - Yang, Le-He AU - Yang LH AD - Department of Respiratory Medicine, Wenzhou Medical University, Wenzhou 325600, Zhejiang, People's Republic of China. FAU - Ren, Zhuo-Chao AU - Ren ZC AD - Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, People's Republic of China. FAU - Mu, De-Guang AU - Mu DG AD - Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, People's Republic of China. FAU - Li, Ya-Qing AU - Li YQ AD - Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, People's Republic of China. FAU - Yan, Jian-Ping AU - Yan JP AD - Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, People's Republic of China. FAU - Wang, Liang-Xing AU - Wang LX AD - Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, People's Republic of China. FAU - Chen, Chun AU - Chen C AD - Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, People's Republic of China. LA - eng PT - Journal Article DEP - 20190527 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - Q369O8926L (Resveratrol) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Chemokine CCL2/*biosynthesis/metabolism MH - Down-Regulation/*drug effects MH - Endothelial Cells/*drug effects/metabolism/pathology MH - Male MH - Pulmonary Artery/*drug effects/metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Resveratrol/*pharmacology MH - Signal Transduction/*drug effects MH - Tumor Necrosis Factor-alpha/*metabolism MH - p38 Mitogen-Activated Protein Kinases/*metabolism PMC - PMC6549410 OTO - NOTNLM OT - inflammation OT - pulmonary artery endothelial cells OT - pulmonary hypertension OT - pulmonary thromboembolism OT - resveratrol COIS- The authors report no conflicts of interest in this work. EDAT- 2019/06/20 06:00 MHDA- 2019/12/24 06:00 PMCR- 2019/05/27 CRDT- 2019/06/20 06:00 PHST- 2018/08/21 00:00 [received] PHST- 2019/03/04 00:00 [accepted] PHST- 2019/06/20 06:00 [entrez] PHST- 2019/06/20 06:00 [pubmed] PHST- 2019/12/24 06:00 [medline] PHST- 2019/05/27 00:00 [pmc-release] AID - 184785 [pii] AID - 10.2147/DDDT.S184785 [doi] PST - epublish SO - Drug Des Devel Ther. 2019 May 27;13:1843-1853. doi: 10.2147/DDDT.S184785. eCollection 2019.