Study summary · research use only
AICAR suppresses TNF-α-induced complement factor B in RPE cells
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This in vitro study, using ARPE-19 cells and human primary retinal pigment epithelial (RPE) cells, examined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide riboside) on TNF-α-induced complement factor B (CFB) expression. The abstract reports AICAR inhibited TNF-α-induced CFB expression in ARPE-19 and human primary RPE cells in a dose-dependent fashion, and that dipyridamole, which blocks AICAR cellular uptake, abolished this effect. In contrast, the adenosine kinase inhibitor 5-iodotubericidin, which inhibits conversion of AICAR to ZMP, did not reverse the effect on CFB expression, and knockout of AMPK using CRISPR/Cas9 also did not abolish AICAR's inhibitory effect, suggesting an AMPK-independent mechanism.
Abstract
Age related macular degeneration is the leading cause of blindness in the developed world. Although its precise cause remains elusive, dysfunction of the retinal pigment epithelium (RPE) and dysregulation of complement have been implicated in its pathogenesis. The goal of this study was to evaluate the role of an AMP-dependent kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide riboside (AICAR), on tumor necrosis factor alpha (TNF-α) induction of complement factor B (CFB) in RPE cells. We found that AICAR inhibited TNF-α-induced CFB expression in ARPE-19 and human primary RPE cells in a dose-dependent fashion. Treatment of cells with dipyridamole, which blocks AICAR cellular uptake abolished these effects. In contrast, the adenosine kinase inhibitor, 5-iodotubericidin, which inhibits the conversion of AICAR to the direct activator of AMPK, ZMP, did not reverse the effects on TNF-α-induced CFB expression, suggesting AMPK-independent effects. Indeed, knockout of AMPK in RPE cells using Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/Cas9 did not abolish the inhibitory effects of AICAR on RPE CFB expression. Collectively, our results suggest that AICAR can suppress TNF-α-induced CFB expression in RPE cells in an AMPK-independent mechanism, and could be used as a therapeutic target in certain complement over-activation scenarios.
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