title: Gradual inhibition of inducible nitric oxide synthase but not of interleukin-1 beta production in rat microglial cells of endotoxin-treated mixed glial cell cultures.
abstract: In cultures of purified microglial cells and astrocytes from newborn rats, the immunocytochemical localization of interleukin-1 beta (IL-1 beta) and inducible nitric oxide synthase (iNOS) using recently developed antibodies, as well as the release of IL-1 beta and nitric oxide (NO), was studied following exposure of the cells to endotoxin [lipopolysaccharide (LPS)]. In the absence of LPS, IL-1 beta- and iNOS-immunoreactive microglial cells and IL-1 beta or NO release were not observed, whereas in the presence of the endotoxin, the production of NO and IL-1 beta by microglial cells dramatically exceeded their synthesis and release by astrocytes. Interestingly, microglial cells cultured for 4-8 days in the presence of astrocytes appeared to lose their ability to produce iNOS, whereas the release of IL-1 beta remained unaltered. Moreover, endotoxin-stimulated microglial cells appeared to regain their ability to synthesize iNOS following their separation from astrocytes. These data show that microglia are primarily responsible for NO and IL-1 beta production in mixed glial cell cultures upon endotoxin stimulation. Moreover, in the presence of astrocytes the induction of iNOS, but not that of IL-1 beta in microglial cells is gradually inhibited.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Free University, Amsterdam, The Netherlands.
authors.forename: V A
authors.initials: VA
authors.lastname: Vincent
authors.forename: A M
authors.initials: AM
authors.lastname: Van Dam
authors.forename: J H
authors.initials: JH
authors.lastname: Persoons
authors.forename: K
authors.initials: K
authors.lastname: Schotanus
authors.forename: H W
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: A N
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: F
authors.initials: F
authors.lastname: Berkenbosch
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D004731:Endotoxins; D007375:Interleukin-1; D019001:Nitric Oxide Synthase