| First Author | Bai Y | Year | 2014 |
| Journal | Neurosci Lett | Volume | 571 |
| Pages | 5-10 | PubMed ID | 24780563 |
| Mgi Jnum | J:214006 | Mgi Id | MGI:5587861 |
| Doi | 10.1016/j.neulet.2014.04.025 | Citation | Bai Y, et al. (2014) TLR2 signaling directs NO-dependent MMP-9 induction in mouse microglia. Neurosci Lett 571:5-10 |
| abstractText | Microglia are neural immune cells that produce pro-inflammatory proteins in the central nervous system. Dysregulation of microglia gene expression is linked to the chronic brain inflammation and the neurological disorders. Matrix metalloproteinase-9 (MMP-9) is a pro-inflammatory protease that regulates the neurotoxicity of glial cells in the brain and spinal cord. Recent studies showed the accumulation of MMP-9 at microglia-rich plaques associates with neurodegenerative diseases. However, the regulatory mechanism of MMP-9 expression in microglia inflammation is still unknown. Here we show that oxidized low-density lipoprotein (oxLDL) induces the expression and secretion of Pro-MMP-9 (92kDa) via TLR2 signaling pathway in mouse microglial cells. Depletion of TLR2 or its signaling mediators MyD88/TRAF6 blocks the agonist-induced MMP-9 expression. In addition, TLR2-dependent nitric oxide (NO) synthesis is also required for endogenous Pro-MMP-9 expression and secretion. Cell death assay indicates that the neurotoxicity of microglia is regulated by endogenous NO and TLR2 signaling pathway. Our findings establish a pathophysiological link between oxLDL and MMP-9 expression in microglia-related neuroinflammation. |
