PMID- 21355876
OWN - NLM
STAT- MEDLINE
DCOM- 20110901
LR  - 20161125
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 50
IP  - 4
DP  - 2011 May
TI  - Melatonin protects liver against ischemia and reperfusion injury through 
      inhibition of toll-like receptor signaling pathway.
PG  - 403-11
LID - 10.1111/j.1600-079X.2011.00858.x [doi]
AB  - This study investigated the immunomodulating effect of melatonin on toll-like 
      receptor (TLR)-stimulated signal transduction. Rats were subjected to 60 min of 
      ischemia followed by 1 or 5 hr of reperfusion. Melatonin (10 mg/kg) or the 
      vehicle was administered intraperitoneally 15 min prior to ischemia and 
      immediately before reperfusion. Melatonin treatment significantly reduced the 
      level of serum alanine aminotransferase activity. Increased levels of TLR3 and 
      TLR4 protein expression induced by ischemia/reperfusion (I/R) were attenuated by 
      melatonin. Serum level of high-mobility group box 1 (HMGB1), a potent alarmin of 
      the TLR system, increased significantly in the I/R group, and melatonin inhibited 
      this release. Melatonin suppressed the increase in myeloid differentiation factor 
      88 (MyD88) protein expression, extracellular signal-regulated kinase (ERK) and 
      c-Jun N-terminal kinase (JNK) phosphorylation and nuclear translocation of 
      nuclear factor kappaB (NF-kappaB) and phosphorylated c-Jun, a component of activator 
      protein 1. The increased level of toll-receptor-associated activator of 
      interferon (TRIF) expression, phosphorylation of interferon (IFN) regulatory 
      factor 3 (IRF3) and serum IFN-beta was attenuated by melatonin. Melatonin attenuated 
      the levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and 
      inducible nitric oxide synthase (iNOS) protein and mRNA expression, while the 
      level of heme oxygenase-1 (HO-1) was augmented. Our results suggest that 
      melatonin ameliorates I/R-induced liver damage by modulation of TLR-mediated 
      inflammatory responses.
CI  - (c) 2011 The Authors. Journal of Pineal Research (c) 2011 John Wiley & Sons A/S.
FAU - Kang, Jung-Woo
AU  - Kang JW
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-Do, Korea.
FAU - Koh, Eun-Ji
AU  - Koh EJ
FAU - Lee, Sun-Mee
AU  - Lee SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110228
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (Interleukin-6)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Liver/*drug effects/*metabolism
MH  - Male
MH  - Melatonin/*pharmacology
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*prevention & control
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptors/*metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
EDAT- 2011/03/02 06:00
MHDA- 2011/09/02 06:00
CRDT- 2011/03/02 06:00
PHST- 2011/03/02 06:00 [entrez]
PHST- 2011/03/02 06:00 [pubmed]
PHST- 2011/09/02 06:00 [medline]
AID - 10.1111/j.1600-079X.2011.00858.x [doi]
PST - ppublish
SO  - J Pineal Res. 2011 May;50(4):403-11. doi: 10.1111/j.1600-079X.2011.00858.x. Epub 
      2011 Feb 28.