PMID- 9930718
OWN - NLM
STAT- MEDLINE
DCOM- 19990211
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 72
IP  - 2
DP  - 1999 Feb
TI  - Cytokine induction of inducible nitric oxide synthase in an oligodendrocyte cell 
      line: role of p38 mitogen-activated protein kinase activation.
PG  - 472-8
AB  - The induction of inducible nitric oxide synthase (iNOS) by proinflammatory 
      cytokines was studied in an oligodendrocyte progenitor cell line in relation to 
      mitogen-activated protein kinase (MAPK) activation and cytokine-mediated 
      cytotoxicity. When introduced individually to cultures of CG4 cells, the 
      cytokines, i.e., tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), 
      and interferon-gamma (IFN gamma), had either minimal (TNF alpha) or no (IL-1 and 
      IFN gamma) detectable stimulatory effect on the production of nitric oxide. 
      However, combinations of these factors, in particular, TNF alpha plus IFN gamma, 
      elicited a strong enhancement of nitric oxide synthesis and, as revealed by 
      western blot and RT-PCR analysis, the expression of iNOS. TNF alpha and IL-1 were 
      able to activate p38 MAPK in a time- and dose-dependent manner and together 
      showed a combinatorial effect. In contrast, IFN gamma neither activated on its 
      own nor enhanced the activation of p38 MAPK in response to TNF alpha and IL-1. 
      However, a specific inhibitor of p38 MAPK, i.e., SB203580, inhibited the 
      induction of iNOS in cytokine combination-treated cells in a dose-dependent 
      manner, thereby suggesting a role for the MAPK cascade in regulating the 
      induction of iNOS gene expression in cytokine-treated cells. Blocking of nitric 
      oxide production by an inhibitor of iNOS, i.e., nitro-L-arginine methyl ester, 
      had a minimal protective effect against cytokine-mediated cytotoxicity that 
      occurred before the elevation of nitric oxide levels, thereby indicating temporal 
      and functional dissociation of nitric oxide production from cell killing.
FAU - Bhat, N R
AU  - Bhat NR
AD  - Department of Neurology, Medical University of South Carolina, Charleston 29425, 
      USA.
FAU - Zhang, P
AU  - Zhang P
FAU - Bhat, A N
AU  - Bhat AN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Culture Media)
RN  - 0 (Cytokines)
RN  - 0 (Cytotoxins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-1)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Cell Line
MH  - Culture Media/pharmacology
MH  - Cytokines/*pharmacology
MH  - Cytotoxins/pharmacology
MH  - Enzyme Activation/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Imidazoles/pharmacology
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-1/pharmacology
MH  - *Mitogen-Activated Protein Kinases
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*genetics/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Oligodendroglia/cytology/drug effects/*enzymology
MH  - Phosphorylation
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/analysis
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/02/04 00:00
MHDA- 1999/02/04 00:01
CRDT- 1999/02/04 00:00
PHST- 1999/02/04 00:00 [pubmed]
PHST- 1999/02/04 00:01 [medline]
PHST- 1999/02/04 00:00 [entrez]
AID - 10.1046/j.1471-4159.1999.0720472.x [doi]
PST - ppublish
SO  - J Neurochem. 1999 Feb;72(2):472-8. doi: 10.1046/j.1471-4159.1999.0720472.x.