論文 - 詳細
| RRC ID | 56046 |
|---|---|
| 著者 | Ohkuro M, Kim JD, Kuboi Y, Hayashi Y, Mizukami H, Kobayashi-Kuramochi H, Muramoto K, Shirato M, Michikawa-Tanaka F, Moriya J, Kozaki T, Takase K, Chiba K, Agarwala KL, Kimura T, Kotake M, Kawahara T, Yoneda N, Hirota S, Azuma H, Ozasa-Komura N, Ohashi Y, Muratani M, Kimura K, Hishinuma I, Fukamizu A. |
| タイトル | Calreticulin and integrin alpha dissociation induces anti-inflammatory programming in animal models of inflammatory bowel disease. |
| ジャーナル | Nat Commun |
| Abstract |
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD. |
| 巻・号 | 9(1) |
| ページ | 1982 |
| 公開日 | 2018-5-17 |
| DOI | 10.1038/s41467-018-04420-4 |
| PII | 10.1038/s41467-018-04420-4 |
| PMID | 29773794 |
| PMC | PMC5958137 |
| MeSH | Animals Anti-Inflammatory Agents / pharmacology* Anti-Inflammatory Agents / therapeutic use Calreticulin / antagonists & inhibitors Calreticulin / immunology* Colitis, Ulcerative / chemically induced Colitis, Ulcerative / drug therapy Colitis, Ulcerative / immunology* Colon / cytology Colon / immunology Colon / pathology Cyclohexanes / pharmacology* Cyclohexanes / therapeutic use Dextran Sulfate / toxicity Disease Models, Animal Female Healthy Volunteers Humans Integrin alpha Chains / immunology* Integrin alpha Chains / metabolism Jurkat Cells Male Mice Mice, Inbred BALB C Mice, SCID Neutrophil Infiltration / drug effects Neutrophil Infiltration / immunology Neutrophils / drug effects Neutrophils / immunology Piperazines / pharmacology* Piperazines / therapeutic use Protein Binding T-Lymphocytes / drug effects T-Lymphocytes / immunology |
| IF | 11.878 |
| 引用数 | 5 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 22 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Jurkat |