PMID- 18505446
OWN - NLM
STAT- MEDLINE
DCOM- 20090116
LR  - 20220318
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 35
IP  - 9
DP  - 2008 Sep
TI  - Inhibition of toll-like receptor-4, nuclear factor-kappaB and mitogen-activated 
      protein kinase by lignocaine may involve voltage-sensitive sodium channels.
PG  - 1052-8
LID - 10.1111/j.1440-1681.2008.04962.x [doi]
AB  - We have shown previously that lignocaine inhibits the upregulation of inducible 
      nitric oxide synthase (iNOS), a crucial factor that initiates the systemic 
      inflammatory response during sepsis, possibly through voltage-sensitive sodium 
      channels (VSSC). Toll-like receptor-4 (TLR-4), nuclear factor (NF)-kappaB and 
      mitogen activated protein kinases (MAPKs) participate in the upstream regulation 
      of iNOS expression induced by endotoxin. In the present study, we investigated 
      the effects of lignocaine in the regulation of the expression of these enzymes. 
      The role of VSSC in the effects of lignocaine was also investigated. Confluent 
      murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide 
      (LPS; 100 ng/mL), LPS + lignocaine (50 micromol/L), LPS + tetrodotoxin (TTX; 1 
      micromol/L; a VSSC inhibitor), LPS + lignocaine + veratridine (Ver; 50 
      micromol/L; a VSSC activator) or LPS + TTX + Ver. After reacting with LPS for 0, 
      15, 30, 45 and 60 min, cell cultures were harvested and enzyme expression was 
      evaluated. We found that LPS significantly increased the concentrations of TLR-4, 
      NF-kappaB and MAPKs, including extracellular regulated kinase (ERK), c-jun 
      N-terminal kinase (JNK) and p38 MAPK, in activated macrophages. Lignocaine and 
      TTX significantly attenuated the effects of LPS on TLR-4, NF-kappaB, ERK and p38 
      MAPK expression, but not on JNK. Veratridine mitigated the effects of lignocaine 
      and TTX. These data demonstrate that lignocaine has significant inhibitory 
      effects on the activation of TLR-4, NF-kappaB and MAPKs in activated macrophages. 
      Moreover, these effects involve VSSC.
FAU - Lee, Ping-Ying
AU  - Lee PY
AD  - Department of Cardiology Mackay Memorial Hospital, Taipei, Taiwan.
FAU - Tsai, Pei-Shan
AU  - Tsai PS
FAU - Huang, Ya-Hsien
AU  - Huang YH
FAU - Huang, Chun-Jen
AU  - Huang CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080525
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Anesthetics, Local)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Sodium Channels)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 98PI200987 (Lidocaine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Anesthetics, Local/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Enzyme Activation/drug effects
MH  - Lidocaine/*pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Sodium Channels/metabolism/*physiology
MH  - Tetrodotoxin/pharmacology
MH  - Toll-Like Receptor 4/*antagonists & inhibitors
EDAT- 2008/05/29 09:00
MHDA- 2009/01/17 09:00
CRDT- 2008/05/29 09:00
PHST- 2008/05/29 09:00 [pubmed]
PHST- 2009/01/17 09:00 [medline]
PHST- 2008/05/29 09:00 [entrez]
AID - CEP4962 [pii]
AID - 10.1111/j.1440-1681.2008.04962.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2008 Sep;35(9):1052-8. doi: 
      10.1111/j.1440-1681.2008.04962.x. Epub 2008 May 25.