title: Induction of matrix metalloproteinase-3 (MMP-3) expression in the microglia by lipopolysaccharide (LPS) via upregulation of glycoprotein nonmetastatic melanoma B (GPNMB) expression.
abstract: 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.
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, 710069, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Shi
authors.forename: Shuangyan
authors.initials: S
authors.lastname: Duan
authors.forename: Jihong
authors.initials: J
authors.lastname: Cui
authors.forename: Xingrong
authors.initials: X
authors.lastname: Yan
authors.forename: Hongmin
authors.initials: H
authors.lastname: Li
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Fulin
authors.initials: F
authors.lastname: Chen
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
mesh_terms: D000818:Animals; D002460:Cell Line; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse