Intracellular Signaling Mechanisms Involved in LPS-induced Microglial Activation

Abstract

Microglia activated within the injured nervous system further aggravate injuries. To study intracellular signal mechanisms underlying microglial activation, we cultured microglila obtained from I --3-day-old rat brains and activated them with a bacterial endotoxin, 500 ng/ml of lipopolysaccharide (LPS) for 2 days

The activated microglia underwent morphological changes from small and round or ramified cell bodies to large and flat ones. The activated microglia induced nitric oxide synthase (iNOS), resulting in nitric oxide (NO) release. However, both the morphological changes and iNOS induction were completely blocked if either 30 uM genestein, a tyrosine kinase inhibitor or 1 uM Go, a protein kinase C inhibitor was added concomitantly with LPS. These results suggest that tyrosine kinase and protein kinase C are involved in LPS-induced microglial activation.