[Visfatin upregulates MMP-2 and MMP-9 expressions in human monocytes through activating NF-kappaB].

ABSTRACT

OBJECTIVE: To investigate the effects of visfatin on the MMP-2 and MMP-9 expressions in human monocytes and related mechanisms. METHODS: Human monocytes were isolated from blood, the expressions of MMP-2 and MMP-9 at mRNA and protein levels were detected in visfatin stimulated monocytes (0, 100, 200, 400 ng/ml) in the absence and presence of NF-kappaB inhibitor specific Bay11-7082 by Realtime PCR or Western blot, the MMP-2 and MMP-9 enzyme activity in the culture media was also detected by Gelatin Zymography. The NF-kappaB protein level and NF-kappaBp65 expression in visfatin stimulated cells were measured by Western blot and ELISA, respectively. RESULTS: Visfatin upregulated MMP-2 and MMP-9 expressions in human monocytes in a dose dependent manner. After treatment with visfatin 400 ng/ml for 24 h, comparing with the free visfatin treatment, the protein expressions of MMP-2 and MMP-9 were up-regulated to 1.644 +/- 0.052 and 3.578 +/- 0.081 (all P < 0.001); the enzyme activities of MMP-2 and MMP-9 were enhanced by 1.661 +/- 0.036 (P < 0.001) and 1.662 +/- 0.100 (P < 0.001). NF-kappaB was also activated in these cells by visfatin and these effects could be significantly attenuated by Bay11-7082. Visfatin induced a dose-dependent (100 - 400 ng) increase of NF-kappaBp65 nuclear translocation from 0.763 +/- 0.056 to 1.290 +/- 0.065 at 100 and 400 ng/ml, comparing with free visfatin treatment 0.467 +/- 0.046 (all P < 0.05). Bay11-7082 decreased the protein expression of MMP-2 and MMP-9 to 1.183 +/- 0.030 and 2.024 +/- 0.056 (all P < 0.001 comparing with 400 ng/ml visfatin treatment). CONCLUSION: Visfatin enhanced the expression and activity of MMP-2 and MMP-9 in human monocytes via activating NF-kappaB signaling pathway.