PMID- 22288937
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20200914
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 53
IP  - 1
DP  - 2012 Aug
TI  - Melatonin inhibits type 1 interferon signaling of toll-like receptor 4 via heme 
      oxygenase-1 induction in hepatic ischemia/reperfusion.
PG  - 67-76
LID - 10.1111/j.1600-079X.2012.00972.x [doi]
AB  - The cytoprotective mechanisms of melatonin in hepatic ischemia/reperfusion (I/R) 
      injury associated with heme oxygenase-1 (HO-1) induction and type 1 interferon 
      (IFN) signaling pathway downstream of toll-like receptor 4 (TLR4) were 
      investigated. Rats were subjected to 60min of ischemia followed by 5-hr 
      reperfusion. Melatonin (10mg/kg) or vehicle (5% ethanol in saline) was 
      administered intraperitoneally 15min prior to ischemia and immediately before 
      reperfusion. Rats were pretreated with zinc protoporphyrin (ZnPP, 10mg/kg, i.p.), 
      a HO-1 inhibitor, at 16 and 3hr prior to ischemia. Melatonin attenuated the 
      I/R-induced increase in serum alanine aminotransferase activity, and ZnPP 
      reversed this attenuation. Melatonin augmented the levels of HO activity and HO-1 
      protein and mRNA expression, and this enhancement was reversed by ZnPP. Melatonin 
      enhanced the level of NF-E2-related factor-2 (Nrf2) nuclear translocation, and 
      ZnPP reversed this increase. Overexpression of TLR4 and its adaptor proteins, 
      toll-receptor-associated activator of interferon (TRIF), and myeloid 
      differentiation factor 88 (MyD88), induced by I/R, was attenuated by melatonin; 
      ZnPP reversed the effect of melatonin on TLR4 and TRIF expression. Melatonin 
      suppressed the increased interaction between TLR4/TRIF and TLR4/MyD88, which was 
      reversed by ZnPP. Melatonin attenuated the increased levels of JAK2 and STAT1 
      activation as well as IFN-beta, and ZnPP reversed these inhibitory effects of 
      melatonin. Melatonin inhibited the level of chemokine (C-X-C motif) ligand 10 
      (CXCL-10), and ZnPP reversed this inhibition. Our findings suggest that melatonin 
      protects the liver against I/R injury by HO-1 overexpression, which suppresses 
      the type 1 IFN signaling pathway downstream of TLR4.
CI  - (c) 2012 John Wiley & Sons A/S.
FAU - Kang, Jung-Woo
AU  - Kang JW
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
FAU - Lee, Sun-Mee
AU  - Lee SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120131
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Cxcl10 protein, rat)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Myd88 protein, rat)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Protoporphyrins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Ticam1 protein, rat)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 15442-64-5 (zinc protoporphyrin)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Hmox1 protein, rat)
RN  - EC 2.7.10.2 (Jak2 protein, rat)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Adaptor Proteins, Vesicular Transport
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Cell Nucleus/metabolism/pathology
MH  - Chemokine CXCL10/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Heme Oxygenase (Decyclizing)/antagonists & inhibitors/*metabolism
MH  - Interferon-beta/*metabolism
MH  - Janus Kinase 2/metabolism
MH  - Liver/*metabolism/pathology
MH  - Male
MH  - Melatonin/*pharmacology
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Protoporphyrins/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*metabolism/pathology/*prevention & control
MH  - STAT1 Transcription Factor/metabolism
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptor 4/*metabolism
EDAT- 2012/02/01 06:00
MHDA- 2012/11/14 06:00
CRDT- 2012/02/01 06:00
PHST- 2012/02/01 06:00 [entrez]
PHST- 2012/02/01 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
AID - 10.1111/j.1600-079X.2012.00972.x [doi]
PST - ppublish
SO  - J Pineal Res. 2012 Aug;53(1):67-76. doi: 10.1111/j.1600-079X.2012.00972.x. Epub 
      2012 Jan 31.