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

Abstract

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) α and γ, 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 α and γ, 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 α/γ mRNA and protein expression was increased, respectively, and PPAR α/γ 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 PGE 2 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 α agonist or PPAR γ 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 PPARα/γ and COX-2/mPGES-1-mediated pathways and the two pathways might be partly overlapped and even be interrelated.