Endoplasmic reticulum aminopeptidase-1 mediates leukemia inhibitory factor-induced cell surface human leukocyte antigen-G expression in JEG-3 choriocarcinoma cells
Autor: | Seiji Nomura, Tomomi Ito, Kazuhiko Ino, Seiji Sumigama, Masafumi Tsujimoto, Shigehiko Mizutani, Fumitaka Kikkawa, Akira Hattori, Eiko Yamamoto, Fumi Shido, Atsuo Itakura |
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Rok vydání: | 2006 |
Předmět: |
medicine.medical_specialty
Cell Antigen presentation Biology Endoplasmic Reticulum Aminopeptidases Leukemia Inhibitory Factor Minor Histocompatibility Antigens Endocrinology Antigen HLA Antigens Internal medicine medicine Tumor Cells Cultured Humans Secretion Choriocarcinoma RNA Small Interfering reproductive and urinary physiology HLA-G Antigens Antigen Presentation Interleukin-6 Endoplasmic reticulum Decidua Cell Membrane Histocompatibility Antigens Class I Molecular biology Trophoblasts medicine.anatomical_structure Cell culture embryonic structures Female Leukemia inhibitory factor |
Zdroj: | Endocrinology. 147(4) |
ISSN: | 0013-7227 |
Popis: | 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. |
Databáze: | OpenAIRE |
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