Work

Increasing autophagy ameliorates all-trans-retinal-activated NLRP3 inflammasomes in human THP-1 macrophages.

Year: 2023

Type: article

Abstract: OBJECTIVE: -retinal (atRAL). However, the underlying mechanism thereof remains elusive. This study investigated the effects of atRAL on the macrophage cell line THP-1 and determined the underlying signaling pathway through pharmacological and genetical manipulation. METHODS: Red staining. Autophagy was assessed with the LC3BII turnover assay and tandem mCherry-eGFP-LC3B fluorescence microscopy. RESULTS: The maturation and release of IL-1β were regulated by the activation of the NLRP3 inflammasome. Mitochondria-associated ROS were involved in the regulation of NLRP3 inflammasome activation and caspase-1 cleavage. In addition, atRAL functionally activated autophagy in THP-1 cells, and atRAL-induced NLRP3 inflammasome activation was suppressed by autophagy. CONCLUSIONS: atRAL activates both the NLRP3 inflammasome and autophagy in THP-1 cells, and the increasing level of autophagy leads to the inhibition of excessive NLRP3 inflammasome activation. These findings shed new light on the pathogenesis of age-related retinal degeneration.

Source: PubMed Central