PMID- 17604001
OWN - NLM
STAT- MEDLINE
DCOM- 20070823
LR  - 20181228
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 360
IP  - 2
DP  - 2007 Aug 24
TI  - Suppression of cytokine response by GATA inhibitor K-7174 via unfolded protein 
      response.
PG  - 470-5
AB  - K-7174, a GATA-specific inhibitor, is a putative anti-inflammatory agent that 
      attenuates effects of inflammatory cytokines in certain cell types. However, 
      molecular mechanisms involved have not been elucidated. We found that, in 
      glomerular podocytes, induction of monocyte chemoattractant protein 1 (MCP-1) and 
      inducible nitric oxide synthase (iNOS) by TNF-alpha was abrogated by K-7174. It 
      was correlated with unexpected induction of unfolded protein response (UPR) 
      evidenced by: (1) induction of endogenous indicators 78 kDa glucose-regulated 
      protein and CCAAT/enhancer-binding protein-homologous protein, and (2) 
      suppression of an exogenous indicator, endoplasmic reticulum stress-repressive 
      alkaline phosphatase. In podocytes, induction of UPR by either tunicamycin, 
      thapsigargin, A23187 or AB5 subtilase cytotoxin completely reproduced the 
      suppressive effect of K-7174. Furthermore, K-7174-elicited UPR abrogated 
      induction of MCP-1 and iNOS not only by TNF-alpha but also by medium conditioned 
      by activated macrophages. These results suggested a novel, UPR-dependent 
      mechanism underlying the anti-inflammatory potential of K-7174.
FAU - Takano, Yosuke
AU  - Takano Y
AD  - Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine 
      and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 
      409-3898, Japan.
FAU - Hiramatsu, Nobuhiko
AU  - Hiramatsu N
FAU - Okamura, Maro
AU  - Okamura M
FAU - Hayakawa, Kunihiro
AU  - Hayakawa K
FAU - Shimada, Tsuyoshi
AU  - Shimada T
FAU - Kasai, Ayumi
AU  - Kasai A
FAU - Yokouchi, Makiko
AU  - Yokouchi M
FAU - Shitamura, Akihiro
AU  - Shitamura A
FAU - Yao, Jian
AU  - Yao J
FAU - Paton, Adrienne W
AU  - Paton AW
FAU - Paton, James C
AU  - Paton JC
FAU - Kitamura, Masanori
AU  - Kitamura M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070626
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Anisoles)
RN  - 0 (Azepines)
RN  - 0 (Cytokines)
RN  - 0 (GATA Transcription Factors)
RN  - 36376CA57N (K 7174)
SB  - IM
MH  - Animals
MH  - Anisoles/*administration & dosage
MH  - Azepines/*administration & dosage
MH  - Cell Line
MH  - Cytokines/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endoplasmic Reticulum
MH  - GATA Transcription Factors/*metabolism
MH  - Mice
MH  - Podocytes/*drug effects/*metabolism
MH  - Protein Denaturation/drug effects
MH  - Protein Folding
EDAT- 2007/07/03 09:00
MHDA- 2007/08/24 09:00
CRDT- 2007/07/03 09:00
PHST- 2007/06/12 00:00 [received]
PHST- 2007/06/15 00:00 [accepted]
PHST- 2007/07/03 09:00 [pubmed]
PHST- 2007/08/24 09:00 [medline]
PHST- 2007/07/03 09:00 [entrez]
AID - S0006-291X(07)01325-3 [pii]
AID - 10.1016/j.bbrc.2007.06.082 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2007 Aug 24;360(2):470-5. doi: 
      10.1016/j.bbrc.2007.06.082. Epub 2007 Jun 26.