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

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 24h, 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 24h and the PGE(2) release was also decreased. The macrophages stimulated with PGE(2) for 24h 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 PPARalpha/gamma and COX-2/mPGES-1-mediated pathways and the two pathways might be partly overlapped and even be interrelated. 2009 Elsevier Masson SAS. All rights reserved.