Proinflammatory Effect of TWEAK/Fn14 Interaction in Human Retinal Pigment Epithelial Cells

被引:9
作者
Ebihara, Nobuyuki [1 ]
Nakayama, Masafumi [2 ]
Tokura, Tomoko [3 ]
Iwatsu, Minoru
Ushio, Hiroko [3 ]
Murakami, Akira
机构
[1] Juntendo Univ, Dept Ophthalmol, Sch Med, Bunkyo Ku, Tokyo 1138431, Japan
[2] Juntendo Univ, Dept Immunol, Sch Med, Tokyo 1138431, Japan
[3] Juntendo Univ, Allergy Res Ctr, Sch Med, Tokyo 1138431, Japan
关键词
Chemokine; Fn14; MAP kinase; Retinal pigment epithelial cells; TWEAK; PROLIFERATIVE DIABETIC-RETINOPATHY; MONOCYTE CHEMOTACTIC PROTEIN-1; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GROWTH-FACTOR; WEAK INDUCER; RPE CELLS; VITREORETINAL DISORDERS; ENDOTHELIAL-CELLS; C CHEMOKINES; MAP KINASE;
D O I
10.3109/02713680903122037
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To investigate the expression and function of fibroblast growth factor-inducible 14 (Fn14) in human retinal pigment epithelial cells. Methods: A human retinal pigment epithelial cell line (RPE cells: ARPE-19) was used. Expression of Fn14 protein was assessed by flow cytometry. An antibody array and ELISA were used to detect chemokines and cytokines in the supernatant of RPE cells cultured with or without stimulation by TWEAK and/or TGF-beta(1). To explore the mechanism by which TWEAK stimulates RPE cells, we investigated phosphorylation of MAP kinase in TWEAK-stimulated cells. We also investigated whether TWEAK induced the migration of RPE cells by performing an in vitro wound assay. Results: RPE cells showed constitutive surface expression of Fn14 protein. FGF, VEGF, and TGF-beta(1) did not induce Fn14 expression by RPE cells. TWEAK increased the production of IL-8 and MCP-1 by RPE cells via Fn14, and TGF-beta 1 augmented TWEAK-induced production of these chemokines. TWEAK induced the phosphorylation of MAP kinase in RPE cells and promoted the migration of these cells via MAP kinase. Conclusion: TWEAK/Fn14 interaction may have proinflammatory effects in RPE cells.
引用
收藏
页码:836 / 844
页数:9
相关论文
共 56 条
[1]   Monocyte chemotactic protein-1 in proliferative vitreoretinal disorders [J].
AbuElAsrar, AM ;
VanDamme, J ;
Put, W ;
Veckeneer, M ;
Dralands, L ;
Billiau, A ;
Missotten, L .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1997, 123 (05) :599-606
[2]   Role of interleukin 8 in the pathogenesis of proliferative vitreoretinopathy [J].
Aksunger, A ;
Or, M ;
Okur, H ;
Hasanreisoglu, B ;
Akbatur, H .
OPHTHALMOLOGICA, 1997, 211 (04) :223-225
[3]  
Bochaton-Piallat ML, 2000, INVEST OPHTH VIS SCI, V41, P2336
[4]  
Briggs MC, 2000, INVEST OPHTH VIS SCI, V41, P3085
[5]   The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity [J].
Campbell, S ;
Michaelson, J ;
Burkly, L ;
Putterman, C .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2004, 9 :2273-2284
[6]  
Capeans C, 1998, RETINA-J RET VIT DIS, V18, P546
[7]   Platelet derived growth factor and fibroblast growth factor basic levels in the vitreous of patients with vitreoretinal disorders [J].
Cassidy, L ;
Barry, P ;
Shaw, C ;
Duffy, J ;
Kennedy, S .
BRITISH JOURNAL OF OPHTHALMOLOGY, 1998, 82 (02) :181-185
[8]   TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis [J].
Chicheportiche, Y ;
Bourdon, PR ;
Xu, HD ;
Hsu, YM ;
Scott, H ;
Hession, C ;
Garcia, I ;
Browning, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (51) :32401-32410
[9]   CORRELATION OF FIBROSIS AND TRANSFORMING GROWTH FACTOR-BETA TYPE-2 LEVELS IN THE EYE [J].
CONNOR, TB ;
ROBERTS, AB ;
SPORN, MB ;
DANIELPOUR, D ;
DART, LL ;
MICHELS, RG ;
DEBUSTROS, S ;
ENGER, C ;
KATO, H ;
LANSING, M ;
HAYASHI, H ;
GLASER, BM .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (05) :1661-1666
[10]   Anti-TWEAK monoclonal antibodies reduce immune cell infiltration in the central nervous system and severity of experimental autoimmune encephalomyelitis [J].
Desplat-Jégo, S ;
Creidy, R ;
Varriale, S ;
Allaire, N ;
Luo, Y ;
Bernard, D ;
Hahm, K ;
Burkly, L ;
Boucraut, J .
CLINICAL IMMUNOLOGY, 2005, 117 (01) :15-23