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

Abstract

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-β₁. 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-β₁ 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-β₁ 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.

KEYWORDS::

• Chemokine
• Fn14
• MAP kinase
• Retinal pigment epithelial cells
• TWEAK

ACKNOWLEDGMENT

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.