Proinflammatory effect of TWEAK/Fn14 interaction in human retinal pigment epithelial cells.
OBJECTIVE
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.


CONCLUSIONS
TWEAK/Fn14 interaction may have proinflammatory effects in RPE cells.
Ebihara
Nobuyuki
N
Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. ebihara@juntendo.ac.jp
Nakayama
Masafumi
M
Tokura
Tomoko
T
Iwatsu
Minoru
M
Ushio
Hiroko
H
Murakami
Akira
A
D002460:Cell Line; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis; D000074049:Cytokine TWEAK; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D000074050:TWEAK Receptor; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D000074049:Cytokine TWEAK; D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D053773:Transforming Growth Factor beta1; D048069:Tumor Necrosis Factors; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D020929:Mitogen-Activated Protein Kinase Kinases