Modulation of NO and cytokines in microglial cells by Cu/Zn-superoxide dismutase

The activation of microglial cells in response to neuropathological stimuli is one of the prominent features of human neurodegenerative diseases. Cytokines such as IL-1 beta and TNF-alpha and inflammation-related enzymes such as inducible nitric oxide synthase are usually induced during the activation of microglial cells. We investigated the modulation of the activation of microglial cell by transfecting a Cu/Zn-SOD cDNA into BV-2 cells. Parental and transfected BV-2 cells were then subjected to LPS stimulation. The results showed that in Cu/Zn-SOD-transfected BV-2 cells, the expression and activity of Cu/Zn-SOD increased. On the other hand, upon activation by LPS, these cells produced less NO, IL-1 beta, and TNF-alpha than the parental microglial cells. This finding suggests that superoxide may be an early signal triggering the induction of cytokines and that the transfected Cu/Zn-SOD may provide a neuroprotective function via suppression of microglial activation. In addition, this approach may provide a rationale for the development of treatments for neurodegenerative diseases. (C) 2001 Elsevier Science Inc.