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Updated: Jun 18, 2026
Characterization of a Novel Human Organotypic Retinal Culture Technique
Published on: June 9, 2021
Proinflammatory effect of TWEAK/Fn14 interaction in human retinal pigment epithelial cells
Nobuyuki Ebihara1, Masafumi Nakayama, Tomoko Tokura
1Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. ebihara@juntendo.ac.jp
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.
Insights
Fibroblast growth factor-inducible 14 (Fn14) is expressed on retinal pigment epithelial cells. TWEAK/Fn14 signaling promotes inflammation and migration in these cells.
Area of Science:
- Ophthalmology
- Cell Biology
- Immunology
Background:
- Retinal pigment epithelial (RPE) cells play critical roles in maintaining retinal health.
- Dysfunction of RPE cells is implicated in various retinal diseases.
- Understanding RPE cell signaling pathways is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the expression and function of fibroblast growth factor-inducible 14 (Fn14) in human RPE cells.
- To determine the role of TWEAK/Fn14 signaling in RPE cell responses.
- To elucidate the downstream signaling mechanisms involved.
Main Methods:
- Human RPE cells (ARPE-19) were utilized.
- Fn14 protein expression was assessed via flow cytometry.
- Chemokine and cytokine production was measured using antibody arrays and ELISA.
- MAP kinase phosphorylation and cell migration were evaluated in response to TWEAK stimulation.
Main Results:
- RPE cells constitutively express Fn14 on their surface.
- TWEAK stimulation upregulated IL-8 and MCP-1 production through Fn14.
- Transforming growth factor-beta 1 (TGF-β1) enhanced TWEAK-induced chemokine production.
- TWEAK promoted RPE cell migration via MAP kinase activation.
Conclusions:
- The TWEAK/Fn14 signaling pathway may contribute to proinflammatory effects in RPE cells.
- This interaction could be a potential target for managing inflammatory retinal conditions.