title: Glutamine-free condition inhibits lipopolysaccharide-induced invasion of BV2 microglial cells by suppressing of matrix metalloproteinase-9 expression.
abstract: Studies showing the mechanisms involved in glutamine (Gln) starvation and regulation of matrix metalloproteinase-9 (MMP-9) expression in microglia are rare, even though MMP-9 plays a crucial role in the proinflammatory microenvironment by degrading the blood-brain barrier. We investigated the effects of Gln on the expression of MMP-9 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Our findings showed that MMP-9 activity is significantly increased in response to LPS under Gln conditions. However, the Gln-free condition substantially inhibited LPS-induced MMP-9 activity and the expression of its corresponding gene. A matrigel invasion assay demonstrated that the Gln-free condition attenuates LPS-induced invasion of BV2 microglial cells. In addition, our results showed that the Gln-free condition diminishes LPS-induced nuclear factor-kappa B (NF-κB) and activator protein (AP)-1 activity, which are transcription factors that potentially regulate the expression of the MMP-9 gene. Taken together, these data suggest that the Gln-free condition inhibits LPS-induced invasion of BV2 microglial cells by suppressing MMP-9 expression, mainly via inhibition of the NF-κB and AP-1 pathway.
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Ara-1 dong, Jeju 690-756, Republic of Korea.
authors.forename: Rajapaksha Gedara Prasad Tharanga
authors.initials: RG
authors.lastname: Jayasooriya
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D005973:Glutamine / Q000502:physiology*; D007202:Indicators and Reagents; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D005973:Glutamine; D012313:RNA; D008156:Luciferases; D020780:Matrix Metalloproteinase 9
keywords: Activator protein-1; Glutamine; Matrix metalloproteinase-9; Microglia; Nuclear factor-κB