Aspirin inhibits MMP-9 mRNA expression and release via the PPAR alpha/gamma and COX-2/mPGES-1-mediated pathways in macrophages derived from THP-1 cells

作者：Xue, J.; Hua, Y. N.; Xie, M. L.^*; Gu, Z. L.

来源：Biomedicine & Pharmacotherapy, 2010, 64(2): 118-123.

DOI：10.1016/j.biopha.2009.04.033

• Aspirin
• Matrix metalloproteinase-9
• Peroxisome proliferator-activated receptor alpha/gamma
• Membranebound prostaglandin E synthase-1
• Cyclooxygenase
• Prostaglandin E-2
• Macrophages

In present study, we investigated the effects of aspirin on matrix metalloproteinase (MMP)-9 mRNA expression and release and its possible mechanisms in macrophages derived from THP-1 cells. The macrophages were divided into different groups and treated with different drugs, the mRNA expression of MMP-9, peroxisome proliferator-activated receptor (PPAR) alpha and gamma, cyclooxygenase (COX)-2, membranebound prostaglandin E synthase (mPGES)-1 in macrophages were examined with reverse-transcription polymerase chain reaction, and the protein expressions of PPAR alpha and gamma, mPGES-1 were detected by Western-blot, the levels of MMP-9 and PGE(2) in cultured supernatants were determined with enzyme-linked immunosorbent assay. The results indicated that after the macrophages were incubated with aspirin for 24 h, the MMP-9 mRNA expression and release were decreased, while the PPAR alpha/gamma mRNA and protein expression was increased, respectively, and PPAR alpha/gamma agonists could also decrease MMP-9 mRNA expression and release. Additionally, the COX-2 mRNA expression, mPGES-1 mRNA and protein expression in macrophages were all decreased after incubation with aspirin for 24 h and the PGE2 release was also decreased. The macrophages stimulated with PGE(2) for 24 h might increase the MMP-9 mRNA expression and release. When PGE(2) plus PPAR alpha agonist or PPAR gamma agonist were simultaneously used, the stimulation of MMP-9 mRNA expression and release by PGE(2) was significantly decreased. It might be concluded that aspirin could inhibit the MMP-9 gene expression and release through the PPAR alpha/gamma and COX-2/mPGES-1-mediated pathways and the two pathways might be partly overlapped and even be interrelated.

• 出版日期2010-2
• 单位苏州大学