Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population and its pathogenesis has been associated with inflammatory damage to retinal pigment epithelial (RPE) cells. Here, we explored the ability of sulforaphane to protect ARPE-19 cells from lipopolysaccharide (LPS)-induced inflammatory injury and elucidated the underlying molecular mechanism.
Methods: Cell viability, apoptosis, inflammation, PWRN2 expression, nuclear transcription factor-kappa B (NF-kB) activity, and the interaction between PWRN2 and the IkBa protein were assessed in RPE cells under- or over-expressing PWRN2 that had been treated with LPS and sulforaphane.
Results: Overexpression of PWRN2 in LPS-treated cells promoted NF-kB activation by interacting with IkBa, thus reducing cell viability. In contrast, PWRN2 downregulation repressed LPS-induced NF-kB activation and apoptosis in RPE cells. Similarly, sulforaphane downregulated PWRN2 and inhibited NF-kB activation in a concentration-dependent manner. Conversely, PWRN2 overexpression or NF-kB upregulation weakened the anti-inflammatory effects of sulforaphane.
Conclusion: Our results suggest that sulforaphane protects RPE cells from LPS-induced inflammatory injury by suppressing the PWRN2/NF-kB pathway.
Keywords: NF-kB; PWRN2; Sulforaphane; age-related macular degeneration; inflammation; retinal pigment epithelial cells.