Upregulation of GRAIL is associated with remission of ulcerative colitis
| Autor: | Shuji Ishii, Jun Wang, Satoshi Egawa, Harumasa Yoshihara, Tatsuya Kanto, Shingo Tsuji, Shinichiro Shinzaki, Jumpei Kondo, Sachiko Nakajima, Hideki Iijima, Masahiko Tsujii, Masakazu Yasumaru, Takanobu Irie, Norio Hayashi, Tsutomu Nishida, Toshiyuki Yoshio, Yoshimi Kakiuchi |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Adolescent Physiology Ubiquitin-Protein Ligases Inflammatory bowel disease Pathogenesis Antigen Downregulation and upregulation Physiology (medical) medicine Humans Leukapheresis Proto-Oncogene Proteins c-cbl RNA Messenger Colitis Cells Cultured Aged Hepatology Ionophores business.industry Ionomycin Gastroenterology T lymphocyte Middle Aged medicine.disease Ulcerative colitis Up-Regulation Repressor Proteins Immunology Colitis Ulcerative Female business |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 295(1) |
| ISSN: | 0193-1857 |
| Popis: | Abrogating tolerance against unidentified antigens is a critical step in the pathogenesis of ulcerative colitis (UC). T cell anergy, one of the main mechanisms of tolerance, has been shown to be induced by E3 ubiquitin ligases, such as gene related to anergy in lymphocytes (GRAIL), Itch, and c-Cbl in mice. However, it is not well known whether these E3 ligases play roles in human diseases. The pathophysiological role of the E3 ligases in patients with UC was investigated. At first, the expression of GRAIL, Itch, and c-Cbl in human anergic T cells was analyzed by quantitative RT-PCR and Western immunoblotting. Next, the mRNA expression of the E3 ligases was analyzed in peripheral CD4+T cells of 20 patients with UC and 10 healthy volunteers (HV). mRNA expression was analyzed in patients with active UC before and after treatment with prednisolone and leukocytapheresis. Anergic human CD4+T cells expressed significantly higher levels of GRAIL, Itch, and c-Cbl than nonanergic cells. GRAIL expression was significantly higher in patients with UC in remission than in patients with active disease and in HV ( P < 0.01). The level of GRAIL expression was also significantly increased in patients with active disease whose clinical activity index scores improved after treatment ( P < 0.05). There were no significant differences in Itch and c-Cbl expression among patients with active UC, patients with UC in remission, and HV. These data suggest that GRAIL plays an important role in maintaining remission in patients with UC. |
| Databáze: | OpenAIRE |
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