Stimulation of microglial migration and aggregation by lipopolysaccharide involves induction of both apoptosis and proinflammatory activation pathways

• Main Authors: Ya-Ting Yang, 楊雅婷
• Other Authors: Yen-Jen Sung
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/79433387545638075590

碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 93 === Microglia, the resident macrophage-like population in the CNS, are highly mobile and reactive under pathophysiological conditions. As the resident macrophage of the brain, microglia provide a graded response to external stimuli, such as lipopolysaccharide (LPS) or β-amyloid (Aβ)��, involving production of proinflammatory cytokines and chemokines, chemotactic response, increased mobility, and phagocytosis. Abnormal activation of microglial cells has been implicated in various neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and multiple scleraosis. The present study examined the effects of the bacterial endotoxin LPS on the migration and activation of microglial cells, and investigated the potential mechanisms. Using a murine microglial cell line, BV-2, we found that these cells not only released nitric oxide (NO) but also formed colonies in response to LPS stimulation. Such migration/aggregation in the formation of microglial colonies involved both cellular and secretory factors. Activated live microglia gathered around and engulfed apoptotic cells after LPS stimulation, as shown by the time-lapse microscopy. The addition of apoptotic cells and/or the LPS-free conditioned media from LPS-stimulated cells to live microglia could induce colony formation. We then studied the roles of proinflammatory factors in the migratory response. In the past data, administration of indomethacin, an inhibitor of cyclooxygenase, resulted in a significant decrease in NO release but a moderate increase in LPS-induced colony formation. By contrast, while the proinflammatory agent interferon-γ increased NO release, it significantly decreased LPS-induced colony formation. Interestingly, transforming growth factor-β (TGF-β), a major anti-inflammatory cytokine, markedly inhibited both the migratory response and NO release upon LPS treatment. This may have important therapeutic ramifications as to using anti-inflammatory approaches to treat various neurodegenerative diseases not only by suppressing proinflammatory mediators but also inhibiting cell migration/aggregation that may exacerbate the detrimental effects of microglia activation. Our results demonstrate that LPS stimulates microglia migration/aggregation, which involved both apoptosis induction and proinflammatory activation and could be suppressed by TGF-β.