Abstract:
:A role for free radicals has been proposed in infectious brain disease, where resident microglia cells upregulate the inducible nitric oxide synthase isoform (iNOS), and thus are capable of producing nitric oxide at enhanced rates. Using the constitutively expressed NADPH oxidase, microglial cells can generate superoxide, which reacts with nitric oxide to form the powerful oxidant peroxynitrite. In a mixed cell culture system of astrocytes and microglial cells, nitrite levels, used as an indicator of nitric oxide production, were elevated after the addition of lipopolysaccharide (LPS) and cytokines. Immunohistochemistry and the NADPH diaphorase technique demonstrated selective localization of the iNOS protein in microglial cells, whereas no iNOS protein or NADPH diaphorase activity was detected in astrocytes. A similar cellular distribution was observed in vivo following injection of LPS and cytokines into the rat striatum. By contrast, LPS and interferon-gamma led to translocation of NF-kappaB in microglia and in astrocytes, demonstrating that both cell types are responsive to the stimulus. Therefore, downstream control in iNOS expression is cell type-specific.
journal_name
Gliajournal_title
Gliaauthors
Possel H,Noack H,Putzke J,Wolf G,Sies Hdoi
10.1002/1098-1136(200010)32:1<51::aid-glia50>3.0.csubject
Has Abstractpub_date
2000-10-01 00:00:00pages
51-9issue
1eissn
0894-1491issn
1098-1136pii
10.1002/1098-1136(200010)32:1<51::AID-GLIA50>3.0.Cjournal_volume
32pub_type
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