PMID- 10601128
OWN - NLM
STAT- MEDLINE
DCOM- 20000119
LR  - 20190722
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 34
IP  - 6
DP  - 1999 Dec
TI  - Salicylate inhibition of extracellular signal-regulated kinases and inducible 
      nitric oxide synthase.
PG  - 1259-64
AB  - The expression of inducible nitric oxide synthase (iNOS) is a characteristic 
      response to inflammation and can be inhibited with sodium salicylate. We used the 
      cytokine-induced iNOS induction in cardiac fibroblasts as a model system in which 
      to test the hypothesis that effects on mitogen-activated protein kinases (MAPKs) 
      may explain the mechanism by which salicylate exerts its anti-inflammatory 
      effects. Tumor necrosis factor-alpha (TNF-alpha) alone can induce extracellular 
      signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase activity in 
      a rapid and transient manner, whereas interferon-gamma (IFN-gamma) can induce 
      only ERK. The inhibition of either the ERK pathway or p38 MAPK activity with 
      selective inhibitors blocked cytokine-induced iNOS protein and nitrite 
      production. Salicylate treatment inhibited iNOS expression induced by TNF-alpha 
      and IFN-gamma and attenuated the phosphorylation of ERK by TNF-alpha and 
      IFN-gamma either alone or in combination. Salicylate had no obvious effect on the 
      activation of p38 MAPK or c-Jun N-terminal kinase. The results showed that 
      salicylate inhibited the phosphorylation of ERK and iNOS expression induced by 
      cytokines in a dose-dependent manner and suggested that salicylate exerts its 
      anti-inflammatory action in part through inhibition of the ERK pathway and iNOS 
      induction.
FAU - Wang, Z
AU  - Wang Z
AD  - Whitaker Cardiovascular Institute and Department of Biochemistry, Boston 
      University School of Medicine, Boston, MA 02118, USA.
FAU - Brecher, P
AU  - Brecher P
LA  - eng
GR  - HL-53471/HL/NHLBI NIH HHS/United States
GR  - HL-55001/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
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 1.14.13.39 (Nos2 protein, rat)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - WIQ1H85SYP (Sodium Salicylate)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cytokines/pharmacology
MH  - Enzyme Induction/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts/cytology/*drug effects/enzymology
MH  - Interferon-gamma/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Myocardium/cytology
MH  - Nitric Oxide Synthase/*antagonists & inhibitors/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Sodium Salicylate/*pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1161/01.hyp.34.6.1259 [doi]
PST - ppublish
SO  - Hypertension. 1999 Dec;34(6):1259-64. doi: 10.1161/01.hyp.34.6.1259.