| 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
|
| リソース情報 |
| ヒト・動物細胞 |
WEHI-3(RCB0035) |
