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Mitochondrial impairment regulates inflammasome activation in human retinal pigment epithelial cells
Author(s) -
Korhonen E.,
Piippo N.,
Hytti M.,
Kaarniranta K.,
Kauppinen A.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.01373
Subject(s) - inflammasome , mitochondrion , secretion , microbiology and biotechnology , lactate dehydrogenase , antimycin a , reactive oxygen species , retinal pigment epithelium , viability assay , retinal , chemistry , cytotoxicity , cell culture , mitochondrial ros , apoptosis , biology , biochemistry , enzyme , in vitro , genetics , receptor
Purpose Dysfunctional mitochondria and excessive inflammasome activation have been shown to play a role in age‐related macular degeneration. The aim of the present study was to investigate whether release of mitochondrial reactive oxygen species ( ROS ) by impaired mitochondria leads to inflammasome activation and further secretion of IL ‐1 β in human retinal pigment epithelial cells. Methods ARPE ‐19 cells were primed with IL ‐1 α and exposed to mitochondrial electron transport chain III inhibitor, Antimycin A, after pretreatment with caspase‐1 inhibitor, Ac‐ YVAD ‐ CMK or mitochondrion‐specific ROS scavenger, mito‐ TEMPO . Pro and mature forms of IL ‐1 β were measured from cell lysates and cell culture supernatants by enzyme linked immunosorbent assay ( ELISA ) method. Cytotoxicity was determined by commercial lactate dehydrogenase ( LDH ) assay. Results Antimycin A induced secretion of mature form of IL ‐1 β in IL ‐1 α primed ARPE ‐19 cells. However, secretion of IL ‐1 β was significantly declined by Ac‐ YVAD ‐ CMK and further by pretreating cells with mito‐ TEMPO . AC ‐ YVAD ‐ CMK or mito‐ TEMPO had no impact to the cell viability. Conclusions In conclusion, the present study reveals that impaired mitochondria increases release of bioactive IL ‐1 β through the inflammasome activation in human retinal pigment epithelial cells.