PMID- 9259476
OWN - NLM
STAT- MEDLINE
DCOM- 19971002
LR  - 20190701
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 230
IP  - 2
DP  - 1997 Jul 18
TI  - The dominant role of exogenous or endogenous interleukin-1 beta on expression and 
      activity of inducible nitric oxide synthase in rat microvascular brain 
      endothelial cells.
PG  - 109-12
AB  - In the brain large amounts of nitric oxide are produced in response to various 
      pathological stimuli such as infectious agents, ischemia and trauma. Although it 
      is known that endothelial cells can express the inducible isoform of nitric oxide 
      synthase (iNOS) upon activation, the impact of different cytokines on iNOS 
      expression in rat microvascular endothelial cells remains unclear. We now 
      investigated iNOS mRNA expression and enzyme activity in primary cell cultures of 
      rat microvascular brain endothelial cells after treatment with the 
      proinflammatory cytokines interleukin-1beta (IL-1beta), Tumor necrosis 
      factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) alone or in 
      combination. Cells were characterized by immunocytochemistry staining for 
      von-Willebrand-factor and the rat brain endothelial antigen recognized by 
      monoclonal antibody Ox2. iNOS-enzyme activity was determined by measurement of 
      nitrite in the supernatants of cell culture using the Griess-reaction. In 
      addition mRNA expression was analysed by RT-PCR with iNOS and IL-1beta specific 
      primers. All cells in the endothelial cell culture were found to express the 
      antigenic phenotype vWF+/Ox2+/Ox43-, thus identifying the cells as rat brain 
      endothelial cells of microvascular origin. IL-1beta was the only cytokine that as 
      a single stimulus induced iNOS mRNA expression and iNOS-enzyme activity in these 
      endothelial cells. All combinations of two cytokines, including that of TNF-alpha 
      and IFN-gamma--or the triple combination led to expression of iNOS-mRNA and 
      active protein. Cell activation by the combination of TNF-alpha + IFN-gamma led 
      to an early expression of IL-1beta by the endothelial cells suggesting iNOS 
      induction as a consequence of endogenous IL-1beta production under this 
      challenge. The experiments prove that rat brain microvascular endothelial cells 
      express iNOS and produce large amounts of NO under inflammatory conditions. 
      Furthermore, our results indicate a decisive role of IL-1beta in iNOS expression 
      and NO generation.
FAU - Bonmann, E
AU  - Bonmann E
AD  - Department of Neurology, Ruprecht-Karls-University, Heidelberg, Germany. 
      EckhardBonmann@krzmail.krz.uniheidelberg.de
FAU - Suschek, C
AU  - Suschek C
FAU - Spranger, M
AU  - Spranger M
FAU - Kolb-Bachofen, V
AU  - Kolb-Bachofen V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Cerebrovascular Circulation
MH  - Endothelium, Vascular/drug effects/*enzymology/immunology
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-1/*pharmacology/*physiology
MH  - *Microcirculation
MH  - Nitric Oxide Synthase/*biosynthesis/metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Proteins/pharmacology
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1997/07/18 00:00
MHDA- 1997/07/18 00:01
CRDT- 1997/07/18 00:00
PHST- 1997/07/18 00:00 [pubmed]
PHST- 1997/07/18 00:01 [medline]
PHST- 1997/07/18 00:00 [entrez]
AID - S0304-3940(97)00485-0 [pii]
AID - 10.1016/s0304-3940(97)00485-0 [doi]
PST - ppublish
SO  - Neurosci Lett. 1997 Jul 18;230(2):109-12. doi: 10.1016/s0304-3940(97)00485-0.