PMID- 9063726
OWN - NLM
STAT- MEDLINE
DCOM- 19970624
LR  - 20191101
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 19
IP  - 3
DP  - 1997 Mar
TI  - Inhibition of endotoxin-induced nitric oxide synthase production in microglial 
      cells by the presence of astroglial cells: a role for transforming growth factor 
      beta.
PG  - 190-8
AB  - In mixed glial cell cultures from cerebral cortices of newborn rats, endotoxin 
      induces inducible nitric oxide (iNOS), nitric oxide (NO), and interleukin-1 beta 
      (IL-1 beta) production in microglial cells. Earlier we demonstrated that 
      endotoxin induced iNOS but not IL-1 beta expression in microglial cells is 
      inhibited by the presence of astroglial cells. In the present paper we describe 
      studies on the mechanism by which astroglial cells exert selective suppressive 
      action on iNOS expression by microglial cells. Expression of iNOS and IL-1 beta 
      was studied by single or double label immunocytochemical techniques and cell 
      identification was performed with GSA-I-B4-isolectin and an antibody against 
      GFAP. Production of IL-1 beta and NO was determined by measurement of IL-1 beta 
      and nitrite concentrations in cell lysates and the culture medium, respectively. 
      TGF beta, a cytokine known to inhibit NO production by endotoxin challenged 
      macrophages, was measured in culture medium of mixed glial cell cultures using a 
      bioassay. Microglial, astroglial, and mixed glial cell cultures produced similar 
      concentrations of TGF beta. The potential effect of TGF beta was studied by using 
      immunoneutralizing antibodies against TGF beta 1 and TGF beta 2 on the induction 
      of iNOS in microglial cells in the presence of astroglial cells. Incubation of 
      the mixed glial cell culture with these TGF beta antibodies (3 micrograms/ml) 
      markedly increased endotoxin-induced NO production and iNOS expression in 
      microglial cells, whereas the production of IL-1 beta was not affected. The 
      antibodies against TGF beta 1 and TGF beta 2 marginally increased NO production 
      in pure microglial cell cultures, nonetheless in cultures of purified microglial 
      cells recombinant TGF beta 1 and TGF beta 2 together with endotoxin inhibited NO 
      production. We conclude that the presence of astroglial cells is essential for 
      the inhibitory effect of TGF beta on NO production by microglial cells (possibly) 
      by activation of TGF beta or by increasing the sensitivity of microglial cells 
      for TGF beta.
FAU - Vincent, V A
AU  - Vincent VA
AD  - Research Institute Neurosciences Vrije Universiteit, Faculty of Medicine, 
      Department of Pharmacology, Amsterdam, The Netherlands.
FAU - Tilders, F J
AU  - Tilders FJ
FAU - Van Dam, A M
AU  - Van Dam AM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Endotoxins)
RN  - 0 (Interleukin-1)
RN  - 0 (Transforming Growth Factor beta)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Astrocytes/*physiology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Endotoxins/pharmacology
MH  - Humans
MH  - Interleukin-1/biosynthesis
MH  - Microglia/cytology/*enzymology
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase/*biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Transforming Growth Factor beta/biosynthesis/*physiology
EDAT- 1997/03/01 00:00
MHDA- 2000/06/20 09:00
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1997/03/01 00:00 [entrez]
AID - 10.1002/(SICI)1098-1136(199703)19:3<190::AID-GLIA2>3.0.CO;2-3 [pii]
AID - 10.1002/(sici)1098-1136(199703)19:3<190::aid-glia2>3.0.co;2-3 [doi]
PST - ppublish
SO  - Glia. 1997 Mar;19(3):190-8. doi: 
      10.1002/(sici)1098-1136(199703)19:3<190::aid-glia2>3.0.co;2-3.