We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Amelioration of lacrimal gland inflammation by oral administration of K-13182 in Sjögren's syndrome model mice.
- Authors
Nishiyama, T.; Mishima, K.; Obara, K.; Inoue, H.; Doi, T.; Kondo, S.; Saka, M.; Tabunoki32, Y.; Hattori, Y.; Kodama, T.; Tsubota, K.; Saito, I.
- 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)-α. 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.
- Subjects
ADHESION; AUTOIMMUNE diseases; BLOOD vessels; CELL lines; CYTOKINES; GROWTH factors; TUMOR necrosis factors
- Publication
Clinical & Experimental Immunology, 2007, Vol 149, Issue 3, p586
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/j.1365-2249.2007.03448.x