RESUMO
Objective To investigate the effects of the leflunomide active metabolite (A771726) on the expression of phorbol-12-myristate-13-acetate (PMA) -induced CD147, matrix metallo-proteinase (MMP)-2 and MMP-9 on THP-1 cells. Methods THP-1 cells were cultured in RPMI-1640 medium supplemented with 10％ fetal bovine serum. For all experiments, THP-1 cells were cultured at an initial density of 5×105/ml. Before A771726 treatment, cells were cultured with serum-free RPMI-1640 medium for 12 h, THP-1cells were co-cultured with PMA at three different concentrations of A771726 (5, 15 , 45 μg/ml) for 24 h.The mRNA expression of CD147, MMP-2 and MMP-9 was measured by real-time PCR. CD147 expression on the cells were evaluated by flow cytometric analysis. The activity of MMP-2 and MMP-9 were evaluated by gelatin zymography. Statistical differences among the groups were tested by one-way ANOVA or KruskalWallis test. Results The expression of CD147, MMP-2 and MMP-9 were upgraded by the PMA. The expression of CD147 on THP-1 cells was inhibited significantly by A771726 in a dose-dependent pattern (P＜0.01). The mean fluorescence intensity (MFI) of CD147 in positive control group was 109.5±3.8, the MFI in A771726 (5, 15, 45 μg/ml) group were 73.3±2.5, 64.5±2.3, 40.9±2.7, respectively. The expression of MMP-2, MMP-9 mRNA and the activity of MMP-2, MMP-9 in the supernatant was inhibited significantly by A771726 (P＜0.01). The expression of CD147 mRNA was not inhibited significantly by A771726 (P＞0.05).Conclusion Leflunomide active metabolite (A771726) can inhibit the expression of PMA-induced CD147,MMP-2 and MMP-9 on THP-1 Cells.
RESUMO
Objective To observe the effect of infliximab combination therapy on the expression of CD147 on the peripheral CD14+ monocytes of active rheumatoid arthritis (RA) patients. Methods Thirty active RA patients who were refractory to MTX treatment were randomized into three groups (group A, B, C) with the proportion of 3:1:1. Group A and B received four or three infusions of infliximab (3 mg/kg), group C received four infusions of placebo. All three groups were added to a stable background of MTX. The mean fluorescence intensity (MFI) of CD147 expression on the peripheral CD14+ monocytes of RA patients and normal healthy controls were detected by flow cytometry analysis. Clinical and laboratory parameters were assessed before each infusion. One-way ANOVA, Kruskal-Wallis the MFI of CD147 expression at week 18 (P<0.05). Marked differences were observed between the infliximab + MTX group and the placebo + MTX group on the change of the MFI of CD147 expression from baseline to week 18 (P<0.05).Conclusion CD147 expression on the peripheral CD14+ monocytes of active RA patients is increased, and combination therapy of infliximab and MTX can inhibit the expression.
