PMID- 16439450
OWN - NLM
STAT- MEDLINE
DCOM- 20060414
LR  - 20161124
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 147
IP  - 4
DP  - 2006 Apr
TI  - Endoplasmic reticulum aminopeptidase-1 mediates leukemia inhibitory 
      factor-induced cell surface human leukocyte antigen-G expression in JEG-3 
      choriocarcinoma cells.
PG  - 1780-8
AB  - Maternal immune tolerance is required for extravillous trophoblasts (EVTs) to 
      invade the decidua without rejection. Endoplasmic reticulum aminopeptidase-1 
      (ERAP1) generates human leukocyte antigen (HLA) class I-adapted antigenic 
      peptides, but its function in trophoblasts lacking classical HLA class I 
      molecules remains undetermined. Leukemia inhibitory factor (LIF) is produced from 
      decidua during the implantation period and plays a necessary role in establishing 
      pregnancy. This study is intended to investigate the location and the function of 
      ERAP1 in trophoblastic cells, focusing on LIF. Immunohistochemistry showed strong 
      ERAP1 expression in cultured EVTs. In choriocarcinoma cell lines used as a model 
      for trophoblasts, ERAP1 was expressed more intensively in JEG-3 than BeWo cells. 
      Immunoblot analysis and immunocytochemistry localized ERAP1 to the endoplasmic 
      reticulum (ER) in JEG-3 cells. Flow cytometry with HLA-G antibody to monitor the 
      supply of antigenic peptides presenting to HLA-G in the ER showed that reducing 
      ERAP1 transcripts by RNA interference did not affect cell surface expression of 
      membrane HLA-G1 (mHLA-G1) in JEG-3 cells under basal conditions. In LIF-treated 
      JEG-3 cells, cell surface mHLA-G1 expression was increased along with ERAP1 
      protein and promoter activities. In contrast to nonstimulated cells, eliminating 
      ERAP1 from LIF-treated JEG-3 cells reduced the cell surface mHLA-G1 expression 
      and soluble HLA-G1 secretion. This study provides the first evidence showing that 
      ERAP1 is localized in the ER of trophoblasts and is involved in regulating cell 
      surface HLA-G expression in the presence of LIF. Consequently, ERAP1 would 
      function to present antigenic peptides to HLA-G in trophoblasts.
FAU - Shido, Fumi
AU  - Shido F
AD  - Department of Obstetrics and Gynecology, Nagoya University Graduate School of 
      Medicine, Japan.
FAU - Ito, Tomomi
AU  - Ito T
FAU - Nomura, Seiji
AU  - Nomura S
FAU - Yamamoto, Eiko
AU  - Yamamoto E
FAU - Sumigama, Seiji
AU  - Sumigama S
FAU - Ino, Kazuhiko
AU  - Ino K
FAU - Itakura, Atsuo
AU  - Itakura A
FAU - Hattori, Akira
AU  - Hattori A
FAU - Tsujimoto, Masafumi
AU  - Tsujimoto M
FAU - Mizutani, Shigehiko
AU  - Mizutani S
FAU - Kikkawa, Fumitaka
AU  - Kikkawa F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060126
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-G Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Interleukin-6)
RN  - 0 (LIF protein, human)
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.- (ERAP1 protein, human)
SB  - IM
MH  - Aminopeptidases/analysis/*physiology
MH  - Antigen Presentation
MH  - Cell Membrane/immunology
MH  - Choriocarcinoma/immunology
MH  - Endoplasmic Reticulum/*enzymology
MH  - Female
MH  - HLA Antigens/*analysis
MH  - HLA-G Antigens
MH  - Histocompatibility Antigens Class I/*analysis
MH  - Humans
MH  - Interleukin-6/*pharmacology
MH  - Leukemia Inhibitory Factor
MH  - Minor Histocompatibility Antigens
MH  - RNA, Small Interfering/pharmacology
MH  - Trophoblasts/enzymology/*immunology
MH  - Tumor Cells, Cultured
EDAT- 2006/01/28 09:00
MHDA- 2006/04/15 09:00
CRDT- 2006/01/28 09:00
PHST- 2006/01/28 09:00 [pubmed]
PHST- 2006/04/15 09:00 [medline]
PHST- 2006/01/28 09:00 [entrez]
AID - en.2005-1449 [pii]
AID - 10.1210/en.2005-1449 [doi]
PST - ppublish
SO  - Endocrinology. 2006 Apr;147(4):1780-8. doi: 10.1210/en.2005-1449. Epub 2006 Jan 
      26.