論文 - 詳細
| RRC ID | 43033 |
|---|---|
| 著者 | Nishiyama T, Mishima K, Obara K, Inoue H, Doi T, Kondo S, Saka M, Tabunoki Y, Hattori Y, Kodama T, Tsubota K, Saito I. |
| タイトル | Amelioration of lacrimal gland inflammation by oral administration of K-13182 in Sjögren's syndrome model mice. |
| ジャーナル | Clin Exp Immunol |
| Abstract |
Regulation of the adhesion of mononuclear cells to endothelial cells is considered to be a critical step for the treatment of inflammatory diseases, including autoimmune diseases. K-13182 was identified as a novel inhibitor for these adhesions. K-13182 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) on human umbilical vein endothelial cells (HUVECs) and on mouse vascular endothelial cell line (MAECs) induced by tumour necrosis factor (TNF)-alpha. K-13182 also inhibited the adhesion of mononuclear cells to these HUVECs and MAECs, indicating that K-13182 suppressed these adhesions mediated by cellular adhesion molecules including VCAM-1. To evaluate the therapeutic effect in autoimmune disease model mice, K-13182 was orally administered to non-obese diabetic (NOD) mice as Sjögren's syndrome (SS) model mice. Severe destructive inflammatory lesions were observed in the lacrimal glands of vehicle-treated control mice; however, 8-week administration of K-13182 inhibited the mononuclear cell infiltration into the inflammatory lesions of the lacrimal glands. In K-13182-treated mice, the decrease in tear secretion was also prevented compared to the control mice. In addition, the apoptosis and the expression of FasL (CD178), perforin, and granzyme A was suppressed in the lacrimal glands of K-13182-treated mice. Therefore, K-13182 demonstrated the possibility of therapeutic efficacy for the inflammatory region of autoimmune disease model mice. These data reveal that VCAM-1 is a promising target molecule for the treatment of autoimmune diseases as a therapeutic strategy and that K-13182 has the potential as a new anti-inflammatory drug for SS. |
| 巻・号 | 149(3) |
| ページ | 586-95 |
| 公開日 | 2007-9-1 |
| DOI | 10.1111/j.1365-2249.2007.03448.x |
| PII | CEI3448 |
| PMID | 17614971 |
| PMC | PMC2219315 |
| MeSH | Administration, Oral Animals Anti-Inflammatory Agents / pharmacology Anti-Inflammatory Agents / therapeutic use* Cell Adhesion / drug effects Cells, Cultured Dacryocystitis / drug therapy* Dacryocystitis / metabolism Dacryocystitis / pathology Disease Models, Animal Dose-Response Relationship, Drug Drug Evaluation, Preclinical Endothelium, Vascular / drug effects Endothelium, Vascular / metabolism Gene Expression Regulation / drug effects Male Mice Mice, Inbred NOD Reverse Transcriptase Polymerase Chain Reaction / methods Sjogren's Syndrome / drug therapy* Sjogren's Syndrome / metabolism Sjogren's Syndrome / pathology Vascular Cell Adhesion Molecule-1 / genetics Vascular Cell Adhesion Molecule-1 / metabolism |
| IF | 3.532 |
| 引用数 | 8 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | WEHI-3(RCB0035) |