PMID- 21633911
OWN - NLM
STAT- MEDLINE
DCOM- 20120605
LR  - 20161020
IS  - 1439-7609 (Electronic)
IS  - 1439-7595 (Linking)
VI  - 22
IP  - 1
DP  - 2012 Feb
TI  - Six-transmembrane epithelial antigen of prostate4 (STEAP4) is a tumor necrosis 
      factor alpha-induced protein that regulates IL-6, IL-8, and cell proliferation in 
      synovium from patients with rheumatoid arthritis.
PG  - 128-36
LID - 10.1007/s10165-011-0475-y [doi]
AB  - Human six-transmembrane epithelial antigen of prostate4 (STEAP4), an ortholog of 
      mouse tumor necrosis factor-alpha-induced adipose-related protein (TIARP), plays a 
      role in tumor necrosis factor (TNF)-dependent arthritis models. However, its role 
      in rheumatoid arthritis (RA) is still obscure. This study explored such a role 
      for STEAP4. The expressions of STEAP4, TNFalpha, and IL-6 were compared in synovia of 
      RA and osteoarthritis patients. STEAP4 induction was examined in TNFalpha-stimulated 
      fibroblast-like synoviocytes (FLS) in vitro. FLS (with/without TNFalpha stimulation) 
      were also analyzed for IL-6 expression after STEAP4 knockdown, using siRNA or 
      transfection with STEAP4-plasmid DNA. IL-8, cell proliferation, and apoptosis 
      were also evaluated in STEAP4-overexpressing FLS. The expression of STEAP4 in 
      joints correlated with TNFalpha expression, specifically in RA synovium. In the 
      cultured FLS, STEAP4 protein expression was augmented by TNFalpha activation, and 
      localized in endosomal/lysosomal compartments. STEAP4 downregulation by siRNA 
      enhanced the expression of IL-6 mRNA, while STEAP4 overexpression suppressed IL-6 
      and IL-8 expression, inhibited cell proliferation, and induced apoptosis via 
      caspase-3. The results indicated that human STEAP4 is regulated by TNFalpha in 
      synovium, where it controls IL-6 secretion and proliferation of FLS, suggesting 
      that STEAP4 might potentially suppress the pathogenesis of TNFalpha-induced arthritis 
      such as RA.
FAU - Tanaka, Yoko
AU  - Tanaka Y
AD  - Division of Clinical Immunology, Doctoral Program in Clinical Science, Graduate 
      School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 
      Tsukuba 305-8575, Japan.
FAU - Matsumoto, Isao
AU  - Matsumoto I
FAU - Iwanami, Keiichi
AU  - Iwanami K
FAU - Inoue, Asuka
AU  - Inoue A
FAU - Minami, Reiko
AU  - Minami R
FAU - Umeda, Naoto
AU  - Umeda N
FAU - Kanamori, Akihiro
AU  - Kanamori A
FAU - Ochiai, Naoyuki
AU  - Ochiai N
FAU - Miyazawa, Keiji
AU  - Miyazawa K
FAU - Sugihara, Makoto
AU  - Sugihara M
FAU - Hayashi, Taichi
AU  - Hayashi T
FAU - Goto, Daisuke
AU  - Goto D
FAU - Ito, Satoshi
AU  - Ito S
FAU - Sumida, Takayuki
AU  - Sumida T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110603
PL  - England
TA  - Mod Rheumatol
JT  - Modern rheumatology
JID - 100959226
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.16.1.- (STEAP4 protein, human)
SB  - IM
MH  - Arthritis, Rheumatoid/genetics/*metabolism/pathology
MH  - Cell Proliferation/drug effects
MH  - Fibroblasts/drug effects/metabolism/pathology
MH  - Gene Expression/drug effects
MH  - Gene Silencing
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Interleukin-8/*metabolism
MH  - Jurkat Cells
MH  - Membrane Proteins/genetics/*metabolism
MH  - Osteoarthritis, Knee/metabolism/pathology
MH  - Oxidoreductases/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/pharmacology
MH  - Synovial Membrane/drug effects/*metabolism/pathology
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism/pharmacology
EDAT- 2011/06/03 06:00
MHDA- 2012/06/06 06:00
CRDT- 2011/06/03 06:00
PHST- 2011/02/10 00:00 [received]
PHST- 2011/05/16 00:00 [accepted]
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2012/06/06 06:00 [medline]
AID - 10.1007/s10165-011-0475-y [doi]
PST - ppublish
SO  - Mod Rheumatol. 2012 Feb;22(1):128-36. doi: 10.1007/s10165-011-0475-y. Epub 2011 
      Jun 3.