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. Cyto kines such as IL-1 beta and TNF-alpha and inflammation-related enzymes such as inducible nitric oxide synthase are usually induced during the activati on 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 res ults showed that in Cu/Zn-SOD-transfected BV-2 cells, the expression and ac tivity of Cu/Zn-SOD increased. On the other hand, upon activation by LPS, t hese cells produced less NO, IL-1 beta, and TNF-alpha than the parental mic roglial cells. This finding suggests that superoxide may be an early signal triggering the induction of cytokines and that the transfected Cu/Zn-SOD m ay provide a neuroprotective function via suppression of microglial activat ion. In addition, this approach may provide a rationale for the development of treatments for neurodegenerative diseases. (C) 2001 Elsevier Science In c.