抄録
Background: Anti-tumor necrosis factor α (anti-TNF-α) agents have been successfully applied for the treatment of rheumatoid arthritis, Crohn's disease, and other chronic inflammatory diseases. Not only the neutralization of soluble TNF-α but also the effect on transmembrane TNF-α is important mechanisms of action of anti-TNF-α agents. This study investigated the cytotoxic effects of new anti-TNF-α agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-α. Methods: Transmembrane TNF-α-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF-α agent to transmembrane TNF-α, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined. Results: Certolizumab pegol and golimumab bound to transmembrane TNF-α. Golimumab induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNF-α-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab. Conclusions: The cytotoxic effects of anti-TNF-α agents on TNF-α-expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNF-α-producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 1224-1231 |
| ページ数 | 8 |
| ジャーナル | Inflammatory Bowel Diseases |
| 巻 | 19 |
| 発行部数 | 6 |
| DOI | |
| 出版物ステータス | 出版済み - 5 1 2013 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Gastroenterology
これを引用
The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factorα. / Ueda, Naoyasu; Tsukamoto, Hiroshi; Mitoma, Hiroki; Ayano, Masahiro; Tanaka, Atsushi; Ohta, Shun Ichiro; Inoue, Yasushi; Arinobu, Yojiro; Niiro, Hiroaki; Akashi, Koichi; Horiuchi, Takahiko.
：: Inflammatory Bowel Diseases, 巻 19, 番号 6, 01.05.2013, p. 1224-1231.研究成果: ジャーナルへの寄稿 › 記事
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TY - JOUR
T1 - The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factorα
AU - Ueda, Naoyasu
AU - Tsukamoto, Hiroshi
AU - Mitoma, Hiroki
AU - Ayano, Masahiro
AU - Tanaka, Atsushi
AU - Ohta, Shun Ichiro
AU - Inoue, Yasushi
AU - Arinobu, Yojiro
AU - Niiro, Hiroaki
AU - Akashi, Koichi
AU - Horiuchi, Takahiko
PY - 2013/5/1
Y1 - 2013/5/1
N2 - Background: Anti-tumor necrosis factor α (anti-TNF-α) agents have been successfully applied for the treatment of rheumatoid arthritis, Crohn's disease, and other chronic inflammatory diseases. Not only the neutralization of soluble TNF-α but also the effect on transmembrane TNF-α is important mechanisms of action of anti-TNF-α agents. This study investigated the cytotoxic effects of new anti-TNF-α agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-α. Methods: Transmembrane TNF-α-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF-α agent to transmembrane TNF-α, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined. Results: Certolizumab pegol and golimumab bound to transmembrane TNF-α. Golimumab induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNF-α-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab. Conclusions: The cytotoxic effects of anti-TNF-α agents on TNF-α-expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNF-α-producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.
AB - Background: Anti-tumor necrosis factor α (anti-TNF-α) agents have been successfully applied for the treatment of rheumatoid arthritis, Crohn's disease, and other chronic inflammatory diseases. Not only the neutralization of soluble TNF-α but also the effect on transmembrane TNF-α is important mechanisms of action of anti-TNF-α agents. This study investigated the cytotoxic effects of new anti-TNF-α agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-α. Methods: Transmembrane TNF-α-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF-α agent to transmembrane TNF-α, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined. Results: Certolizumab pegol and golimumab bound to transmembrane TNF-α. Golimumab induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNF-α-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab. Conclusions: The cytotoxic effects of anti-TNF-α agents on TNF-α-expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNF-α-producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.
UR - http://www.scopus.com/inward/record.url?scp=84879206045&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879206045&partnerID=8YFLogxK
U2 - 10.1097/MIB.0b013e318280b169
DO - 10.1097/MIB.0b013e318280b169
M3 - Article
C2 - 23619715
AN - SCOPUS:84879206045
VL - 19
SP - 1224
EP - 1231
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
SN - 1078-0998
IS - 6
ER -