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.
Chang
S C
SC
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
Kao
M C
MC
Fu
M T
MT
Lin
C T
CT
D000818:Animals; D002460:Cell Line / Q000166:cytology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D017343:Genes, Plant / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000819:agonists / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D019684:Magnoliopsida / Q000201:enzymology / Q000235:genetics; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000819:agonists / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013482:Superoxide Dismutase