| Objective: The purpose of present study was to investigate the effects of aspirin on MMP-2 and MMP-9 expression in cultured mouse celiac macrophages, and the possible mechanisms.Methods: Mouse celiac macrophages were collected and cultured, and then were incubated with aspirin 12.5-200μg/ml for 24 h, respectively. The mRNA expression of MMP-2, MMP-9, TIMP-1, PPARαand PPARγwas examined with RT-PCR, and the levels of MMP-2, MMP-9 and TIMP-1 in cultured supernatant were measured with ELISA. For another part of the study, the cultured cells were pretreated with or without 1μmol/l MK886 and/or 4μmol/l GW9662 for 2 h before incubation with aspirin 50μg/ml, subsequently, MMP-2/9 mRNA expression and MMP-9 protein level were determined by RT-PCR and ELISA, respectively.Results: After cultured mouse celiac macrophages were treated with aspirin 12.5-200μg/ml for 24 h, the MMP-2/9 mRNA expression and release were decreased, while the mRNA expression of PPARαand PPARγwas increased, and the optimal concentration of aspirin was at 50μg/ml (P<0.05 or P<0.01). The TIMP-1 mRNA expression and release were also increased by aspirin, but the optimal concentration of the latter was at 12.5μg/ml(P<0.01). If the cultured mouse celiac macrophages were pretreated with PPARαinhibitor MK886 and/or PPARγinhibitor GW9962 for 2 h before treatment with aspirin 50μg/ml, the inhibition of MMP-2/9 mRNA expression and MMP-9 release was significantly reduced(P<0.05 or P<0.01).Conclusion: Aspirin could inhibit the MMP-2/9 expression and activity in mouse celiac macrophages, and its mechanisms might be mediated by the upregulation of PPARα/γexpression for the inhibition of MMP-2/9 gene expression and MMP-9 release, and by the induction of TIMP-1 gene expression and release for the inhibition of MMP-2/9 activity.
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