CD147 expressed by monocytes, macrophages, and synoviocytes cells can stimulate the production of matrix metalloproteinases (MMPs) associated with the development of rheumatoid arthritis (RA). We investigated the effects of Sinomenine (SIN) on invasion and migration ability and gene expression of CD147, MMP-2, MMP-9 of fibroblast-like synoviocytes cells (FLS) co-cultured with activated human monocytic THP-1 cells (A-THP-1) in vitro. SIN is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum. FLS cells were co-cultured with THP-1 cells which were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Cells were treated with different concentrations of SIN. Invasion and migration ability of cells was tested by transwell assays. Western blot analysis and zymographic analysis were adopted to detect the expression of CD147 and MMPs, respectively. RT-PCR was used to determine the expression of mRNA of CD147, MMP-2, and MMP-9. The invasion and migration ability of the co-cultured cells was significantly inhibited by SIN in a concentration-dependent fashion, and at the same time, the levels of CD147, MMP-2, MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 and 1.00 mM (P < 0.01). Our results point to a possible mechanism of SIN on treatment of RA is the inhibitory effect of SIN on cell invasion and migration ability, which strongly correlates with repressing the expression of CD147, MMP-2, and MMP-9.

Aim:The aim of this study was to investigate the mechanism of the effects of Sinomenine (SIN) on the invasion and migration ability of activated human monocytic THP-1 cells (A-THP-1). Sinomenine is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Cells were treated with different concentrations of SIN. The invasion and migration ability of cells was tested by in vitro transwell assays. The levels of CD147 and MMPs were evaluated by flow cytometric analysis and zymographic analysis, respectively. The mRNA expression of CD147, MMP-2, and MMP-9 was measured by RT-PCR. Results:The invasion and migration ability of A-THP-1 cells was significantly inhibited by SIN in a concentration-dependent fashion; at the same time, the levels of CD147, MMP-2, and MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 mmol/L and 1.00 mmol/L (P<0.01). Conclusion: A possible mechanism of the inhibitory effect of SIN on cell invasion and migration ability is repression of the expression of MMP-2 and MMP-9, which strongly correlates with the inhibition of CD147 activity. IntroductionSinomenine (SIN,7, C 19 H 23 NO 4 ), an alkaloid isolated from the Chinese medicinal plant, Sinomenium acutum, has been utilized to safely treat arthritis for many years. Previous studies have demonstrated that SIN has a variety of pharmacological effects, including anti-inflammatory effects, immunosuppression, and prevention of cartilage destruction [1][2][3][4] . As an immunosuppressive agent, SIN has been used extensively in China for the treatment of rheumatoid arthritis [5,6] .Rheumatoid arthritis (RA) is a systemic, immune and inflammatory disease characterized by joint swelling, synovial inflammation and joint destruction, leading to significant disability [7] . The regulation of cell migration and invasion is a critical process throughout the development of RA.Enhanced migration and invasion of peripheral macrophages contribute to joint destruction in RA by directly degrading the cartilage matrix and indirectly promoting angiogenesis. Elevated gene expression of gelatinase A (also called matrix metalloproteinase-2, MMP-2) and gelatinase B (also called matrix metalloproteinase-9, MMP-9) is critical for the progression of RA [8] .The extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a heavily glycosylated protein containing two immunoglobulin super family domains. It is enriched on the surface of macrophages and is associated with differentiation of human monocytic THP-1 cells when treated with phorbol 12-myristate 13-acetate (PMA). This protein stimulates the production of matrix metalloproteinases (MMPs). CD147 has also been reported to play an important role in the invasion and migration ability of cells in both animal models and cancer patients [9] .Although many in vivo studies have demonstrated that SIN can significantly improve...