DC 欄位 | 值 | 語言 |
dc.contributor | 臺大醫院-內科部;臺大醫學院; | en |
dc.contributor.author | Lu M.-C. | en_US |
dc.contributor.author | Lai N.-S. | en_US |
dc.contributor.author | Yin W.-Y. | en_US |
dc.contributor.author | Yu H.C. | en_US |
dc.contributor.author | Huang H.-B. | en_US |
dc.contributor.author | Tung C.-H. | en_US |
dc.contributor.author | Huang K.-Y. | en_US |
dc.contributor.author | CHIA-LI YU | en_US |
dc.creator | Lu, Ming-Chi;Lai, Ning-Sheng;Yin, Wen-Yao;Yu, Hui-Chun;Huang, Hsien-Bin;Tung, Chien-Hsueh;Huang, Kuang-Yung;Yu, Chia-Li | en |
dc.creator | 余家利 | zh-tw |
dc.date | 2013 | en |
dc.date.accessioned | 2014-02-14T07:26:35Z | - |
dc.date.accessioned | 2018-07-11T07:04:49Z | - |
dc.date.available | 2014-02-14T07:26:35Z | - |
dc.date.available | 2018-07-11T07:04:49Z | - |
dc.date.issued | 2013 | - |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/259421 | - |
dc.description.abstract | In a previous study, we found that anti-citrullinated protein antibodies (ACPAs) enhance nuclear factor (NF)-kappa B activity and tumor necrosis factor (TNF)-alpha production by normal human peripheral blood mononuclear cells (PBMCs) and U937 cells via binding to surface-expressed citrullinated glucose-regulated protein 78 (cit-GRP78). However, the downstream signaling pathways remain unclear after binding. In the present study, we firstly measured the effects of different kinase inhibitors on ACPA-mediated TNF-alpha production from normal PBMCs and monocytes. Then, the native and phosphorylated mitogen-activated protein kinases (MAPKs) were detected in ACPA-activated U937 cells by Western blotting. We also explored the role of the phosphoinositide 3-kinase (PI3K)-Akt pathway in activating I kappa B kinase alpha (IKK-alpha) in ACPA-stimulated U937 cells. Finally, we measured the amount of cit-GRP78 from PBMC membrane extracts in RA patients and controls. We found that MAPK and Akt inhibitors, but not PI3K inhibitor, remarkably suppressed ACPA-mediated TNF-alpha production. Interestingly, ACPAs selectively activated extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK), but not p38 MAPK, in U937 cells. This activation was suppressed by cit-GRP78, but not GRP78. The JNK activation further enhanced the phosphorylation of Akt and IKK-alpha. The expression of cit-GRP78 on cell membrane was higher in RA than normal PBMCs. Taken together; these results suggest that through binding to surface, over-expressed cit-GRP78 on RA PBMCs, ACPAs selectively activate ERK1/2 and JNK signaling pathways to enhance IKK-alpha phosphorylation, which leads to the activation of NF-kappa B and the production of TNF-alpha | en |
dc.format.extent | 107 bytes | - |
dc.format.mimetype | text/html | - |
dc.language | en-us | en |
dc.relation | J. Clin. Immunol., 33(3), 558-566 | en |
dc.relation.ispartof | Journal of Clinical Immunology | en_US |
dc.subject | ACPAs | en |
dc.subject | rheumatoid arthritis | en |
dc.subject | MAPK | en |
dc.subject | JNK | en |
dc.subject | ERK | en |
dc.subject | p38 | en |
dc.subject | Akt | en |
dc.subject | IKK-alpha | en |
dc.title | Anti-citrullinated Protein Antibodies Activated ERK1/2 and JNK Mitogen-activated Protein Kinases via Binding to Surface-expressed Citrullinated GRP78 on Mononuclear Cells | en |
dc.identifier.doi | 10.1007/s10875-012-9841-6 | - |
dc.relation.pages | 558-566 | - |
dc.identifier.uri.fulltext | http://ntur.lib.ntu.edu.tw/bitstream/246246/259421/1/index.html | - |
item.fulltext | with fulltext | - |
item.grantfulltext | open | - |
crisitem.author.dept | Molecular Medicine | - |
crisitem.author.orcid | 0000-0003-4988-0400 | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學系
|