Aspirin suppresses TNF‑α‑induced MMP‑9 expression via NF‑κB and MAPK signaling pathways in RAW264.7 cells

Zhang,Ping; Wu,Chao; Huang,Xiao‑Hui; Shen,Chen‑Lin; Li,Lin; Zhang,Wei; Yao,Cheng‑Zeng

doi:10.3892/etm.2017.5252

Aspirin suppresses TNF‑α‑induced MMP‑9 expression via NF‑κB and MAPK signaling pathways in RAW264.7 cells

Authors:
- Ping Zhang
- Chao Wu
- Xiao‑Hui Huang
- Chen‑Lin Shen
- Lin Li
- Wei Zhang
- Cheng‑Zeng Yao
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Affiliations: Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Pharmacology and Institute of Natural Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, P.R. China
Published online on: October 3, 2017 https://doi.org/10.3892/etm.2017.5252
Pages: 5597-5604

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Abstract

Numerous studies have indicated that the expression of matrix metalloproteinase‑9 (MMP‑9) contributes to the atherosclerotic plaque hemorrhage and rupture. Aspirin, a non‑steroidal anti‑inflammation drug, has been known for its anti‑platelet effect in the prevention of the vascular complications of atherosclerosis. The present study aimed to investigate the pharmacological effects of aspirin on tumor necrosis factor‑α (TNF‑α)‑induced MMP‑9 expression and the underlying molecular mechanisms in murine macrophage RAW264.7 cells. Western blot analysis indicated that the protein level of MMP‑9 was reduced by aspirin in a dose‑dependent manner. In addition, downregulation of MMP‑9 mRNA and activity were detected in aspirin‑treated cells using quantitative polymerase chain reaction and a gelatin zymography assay separately. It was also observed that aspirin has a suppressive effect on the activation of nuclear factor (NF)‑κB and inhibits the phosphorylation of mitogen‑activated protein kinases (MAPKs), including extracellular signal‑regulated kinases 1/2, p38 and c‑Jun N‑terminal kinase. Furthermore, subsequent to inhibition of the MAPK pathway by specific inhibitors (PD98059, SB203580 and SP600125), the expression of MMP‑9 was reduced, indicating that the inhibitory effect of aspirin on MMP‑9 in TNF‑α‑treated RAW264.7 cells may be, at least in part, through suppression of NF‑κB activation and the MAPK pathway. These findings support the notion that aspirin has therapeutic potential application in the prevention and treatment of atherosclerosis disease.

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