Prevention of autophagy activates inflammasome signaling in ARPE-19 cells treated with a proteasome inhibitor

    loading  Checking for direct PDF access through Ovid



Age-related macular degeneration (AMD) is the most prominent cause of severe vision loss in western countries. Inflammation is known to play a central role in the pathogenesis of AMD but the mechanisms are still largerly unknown. Lately, the novel signaling pathway of intracellular multi-protein complexes called inflammasomes has been associated with the disease. In addition to inflammation, decline in the intracellular cleaning systems, i.e. autophagy and proteasomal degradation, is another hallmark of AMD. In the present study, we have studied the cross-talk between NLRP3 inflammasomes and autophagy.


ARPE-19 cells were grown into confluence and exposed to the proteasome inhibitor MG-132. Thereafter, Bafilomycin A was added and the cell cultures were incubated for another 24 hours.


Our results show that the inhibition of lysosome acidification by Bafilomycin A increased the release of inflammasome-related cytokine IL-1b in MG-132-treated ARPE-19 cells. In addition, the amounts of inflammasome receptor and adaptor proteins, i.e. NLRP3 and ASC, respectively, as well as the activity of the executive Caspase-1 enzyme were increased.


Our present results suggest that intracellular protein aggregates could induce the inflammasome activation in ARPE-19 cells especially in circumstances where autophagy is declined.

Related Topics

    loading  Loading Related Articles