PMID- 24056124
OWN - NLM
STAT- MEDLINE
DCOM- 20140715
LR  - 20131202
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 721
IP  - 1-3
DP  - 2013 Dec 5
TI  - Tunicamycin inhibits Toll-like receptor-activated inflammation in RAW264.7 cells 
      by suppression of NF-kappaB and c-Jun activity via a mechanism that is independent of 
      ER-stress and N-glycosylation.
PG  - 294-300
LID - S0014-2999(13)00674-2 [pii]
LID - 10.1016/j.ejphar.2013.09.022 [doi]
AB  - In this study, we investigated the effect of tunicamycin on the production of 
      pro-inflammatory molecules in RAW264.7 macrophage cells in response to 
      lipopolysaccharide (LPS) and Toll-like receptor (TLR) agonists. Tunicamycin 
      caused a reduction in LPS-induced nitric oxide (NO) production and expression of 
      inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta 
      (IL-1beta) and tumor necrosis factor alpha (TNF-alpha). In contrast, other ER 
      stress-inducing chemicals, such as A23187 and thapsigargin (TG), increased 
      LPS-induced COX-2 expression and had no effect on LPS-induced iNOS, TNF-alpha or 
      IL-1beta expression. Furthermore, the inhibitory effect of tunicamycin on 
      LPS-induced inflammation was not influenced by salubrinal, an ER stress 
      inhibitor, suggesting that the anti-inflammatory effect of tunicamycin is 
      independent of ER stress. Tunicamycin also inhibited the expression of 
      inflammatory molecule mRNAs induced by stimulation of TLR2 (with lipoteichoic 
      acid) or TLR3 (with polyinosinic:polycytidylic acid), which do not require 
      myeloid differentiation protein-2 (MD2) for their activation. Moreover, 
      inhibition of LPS-induced iNOS expression was not inhibited by castanospermine, 
      another N-glycosylation inhibitor, suggesting that the inhibitory effect of 
      tunicamycin on LPS-induced iNOS induction is likely independent of MD2 
      N-glycosylation. Tunicamycin inhibited nuclear factor-kappaB (NF-kappaB) activity by 
      suppressing LPS-induced nuclear translocation of p50 and subsequent DNA binding 
      of p50 and p65 to the NF-kappaB site of the iNOS promoter. Tunicamycin also inhibited 
      the transcriptional activity of a cAMP-response element (CRE) reporter, possibly 
      by inhibiting c-Jun activation. Therefore, we conclude that tunicamycin represses 
      TLR-induced inflammation through suppression of NF-kappaB and CRE activity via a 
      mechanism that is independent of ER-stress and N-glycosylation.
CI  - (c) 2013 Published by Elsevier B.V.
FAU - Kim, Song-Yi
AU  - Kim SY
AD  - Department of Physiology and Biophysics, College of Medicine, Inha University, 
      253, Shinheung-Dong, Jung-Ku, Incheon, Republic of Korea.
FAU - Hwang, Ji-Sun
AU  - Hwang JS
FAU - Han, Inn-Oc
AU  - Han IO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130918
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Transcription Factor RelA)
RN  - 11089-65-9 (Tunicamycin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-49-2 (DNA)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclooxygenase 2/genetics
MH  - DNA/metabolism
MH  - Enzyme Activation/drug effects
MH  - Inflammation/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - NF-kappa B p50 Subunit/*metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/genetics
MH  - Toll-Like Receptors/*metabolism
MH  - Transcription Factor RelA/*metabolism
MH  - Tunicamycin/*pharmacology
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - ER stress
OT  - Inflammation
OT  - Tunicamycin
EDAT- 2013/09/24 06:00
MHDA- 2014/07/16 06:00
CRDT- 2013/09/24 06:00
PHST- 2012/12/06 00:00 [received]
PHST- 2013/09/04 00:00 [revised]
PHST- 2013/09/11 00:00 [accepted]
PHST- 2013/09/24 06:00 [entrez]
PHST- 2013/09/24 06:00 [pubmed]
PHST- 2014/07/16 06:00 [medline]
AID - S0014-2999(13)00674-2 [pii]
AID - 10.1016/j.ejphar.2013.09.022 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2013 Dec 5;721(1-3):294-300. doi: 10.1016/j.ejphar.2013.09.022. 
      Epub 2013 Sep 18.