Induction of Matrix Metalloproteinase-3 (MMP-3) Expression in the Microglia by Lipopolysaccharide (LPS) via Upregulation of Glycoprotein Nonmetastatic Melanoma B (GPNMB) Expression

Substantial evidence suggests that inflammation is an important contributor to many neurodegenerative disorders. Activated microglial cells play an important role in releasing pro-inflammatory factors, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) for inducing inflammation. Recently, some reports have suggested that glycoprotein nonmetastatic melanoma B (GPNMB) is highly expressed in microglia after LPS treatment. However, the role of GPNMB in activated microglia is not clearly understood. In this study, we used RT-PCR and Western blotting to detect GPNMB and matrix metalloproteinase-3 (MMP-3) expressions in activated microglia. GPNMB small interfering RNA (siRNA) or MMP-3 inhibitor was applied on microglial BV2 cells, and ELISA was performed to measure the expressions of TNF-α and IL-1β in BV2 cells. Levels of iNOS and NO in BV2 cells were also determined. We found that the levels of GPNMB and MMP-3 were significantly increased in BV2 cells after LPS treatment. Moreover, we found that GPNMB significantly upregulated the expression of MMP-3 in BV2 cells, and high expression of MMP-3 was dependent on the level of GPNMB. Inhibition of GPNMB or MMP-3 expression by GPNMB siRNA or MMP-3 inhibitor dramatically suppressed the expressions of TNF-α, IL-1β, iNOS, and NO in activated microglia. All of these results suggest that GPNMB is involved in the inflammatory responses of microglia.