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.
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.
Vincent
V A
VA
Department of Pharmacology, Faculty of Medicine, Free University, Amsterdam, The Netherlands.
Van Dam
A M
AM
Persoons
J H
JH
Schotanus
K
K
Steinbusch
H W
HW
Schoffelmeer
A N
AN
Berkenbosch
F
F
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
D004731:Endotoxins; D007375:Interleukin-1; D019001:Nitric Oxide Synthase