論文 - 詳細
| RRC ID | 18191 |
|---|---|
| 著者 | Gono T, Takarada T, Fukumori R, Kawaguchi Y, Kaneko H, Hanaoka M, Katsumata Y, Yoneda Y, Yamanaka H. |
| タイトル | NR2-reactive antibody decreases cell viability through augmentation of Ca(2+) influx in systemic lupus erythematosus. |
| ジャーナル | Arthritis Rheum |
| Abstract |
OBJECTIVE:Anti-N-methyl-D-aspartate (anti-NMDA) receptor subunit NR2-reactive antibody may play a crucial role in neuronal manifestations of systemic lupus erythematosus (SLE). However, how NR2-reactive antibody acts as a critical modulator of the NMDA receptor is unknown. This study was undertaken to investigate the biologic function of NR2-reactive antibody in patients with SLE. METHODS:The study included 14 patients with SLE, 9 of whom had NR2-reactive antibody. We analyzed the effects of NR2-reactive antibody on cell viability and intracellular Ca(2+) level. We also investigated the efficacy of zinc as a modulator of the intracellular Ca(2+) level in the presence of NR2-reactive antibody. RESULTS:There was a significant inverse correlation between the NR2-reactive antibody titer and cell viability (R(2) = 0.67, P < 0.0001; n = 23), and there was a significant association between the NR2-reactive antibody titer and the intracellular Ca(2+) level in NR1/NR2a-transfected HEK 293 cells (R(2) = 0.69, P < 0.0001). Intracellular Ca(2+) levels were significantly higher in cells incubated with IgG derived from NR2-reactive antibody-positive SLE patients than in those incubated with IgG derived from NR2-reactive antibody-negative SLE patients (P = 0.0002). The addition of zinc decreased the intracellular Ca(2+) level in a dose-dependent manner. NR2-reactive antibody-positive SLE IgG weakened the efficacy of zinc as a negative modulator of the intracellular Ca(2+) level. CONCLUSION:Our findings indicate that NR2-reactive antibody decreases cell viability by Ca(2+) influx in SLE through inhibition of the binding capacity of zinc. |
| 巻・号 | 63(12) |
| ページ | 3952-9 |
| 公開日 | 2011-12-1 |
| DOI | 10.1002/art.30616 |
| PMID | 22012858 |
| MeSH | Antibodies / blood Antibodies / pharmacology* Antibodies, Antinuclear / blood Calcium / metabolism* Case-Control Studies Cell Survival / drug effects Cell Survival / physiology DNA / immunology Dose-Response Relationship, Drug HEK293 Cells Humans Immunoglobulin G / pharmacology Kidney / cytology Kidney / drug effects* Kidney / embryology Lupus Erythematosus, Systemic / immunology* Lupus Erythematosus, Systemic / metabolism* Lupus Erythematosus, Systemic / physiopathology Receptors, N-Methyl-D-Aspartate / immunology* Zinc / pharmacology |
| 引用数 | 17 |
| WOS 分野 | RHEUMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |