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

• Published in: Biomedicine & pharmacotherapy 2010-02, Vol.64 (2), p.118-123
• Main Authors: Xue, J, Hua, Y.N, Xie, M.L, Gu, Z.L
• Format: Article
• Language: English
• Subjects: Aspirin; Biological and medical sciences; Cyclooxygenase; Internal Medicine; Macrophages; Matrix metalloproteinase-9; Medical Education; Medical sciences; Membranebound prostaglandin E synthase-1; Peroxisome proliferator-activated receptor α/γ; Pharmacology. Drug treatments; Prostaglandin E 2
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2009.04.033

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 PGE2 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 PGE2 release was also decreased. The macrophages stimulated with PGE2 for 24 h might increase the MMP-9 mRNA expression and release. When PGE2 plus PPAR α agonist or PPAR γ agonist were simultaneously used, the stimulation of MMP-9 mRNA expression and release by PGE2 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.