Caspase-8 promotes NLRP3 inflammasome activation mediates eye development defects in zebrafish larvae exposed to perfulorooctane sulfonate (PFOS).
Environ Pollut
; 356: 124252, 2024 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-38815886
ABSTRACT
Epidemiological evidence showed that serum high perfluorooctane sulfonate (PFOS) levels are associated with multiple eye related diseases, but the potential underlying molecular mechanisms remain poorly understood. Zebrafish and photoreceptor cell (661w) models were used to investigate the molecular mechanism of PFOS induced eye development defects. Our results showed a novel molecular mechanism of PFOS-induced inflammation response-mediated photoreceptor cell death associated with eye development defects. Inhibition of Caspase-8 activation significantly decreased photoreceptor cell death in PFOS exposure. Mechanistically, Toll-like receptor 4 (TLR4) mediates activation of Caspase-8 promote activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome to elicit maturation of interleukin-1 beta (IL-1ß) via Caspase-1 activation, facilitating photoreceptor cell inflammation damage in PFOS exposure. In addition, we also made a novel finding that Caspase-3 activation was increased via Caspase-8 activation and directly intensified cell death. Our results show the important role of Caspase-8 activation in PFOS induced eye development defects and highlight Caspase-8 mediated activation of the NLRP3 inflammation triggers activation of Caspase-1 and promote the maturation of IL-1ß in retinal inflammatory injury.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zebrafish
/
Alkanesulfonic Acids
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Caspase 8
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Inflammasomes
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Fluorocarbons
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NLR Family, Pyrin Domain-Containing 3 Protein
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Larva
Limits:
Animals
Language:
En
Journal:
Environ Pollut
Journal subject:
SAUDE AMBIENTAL
Year:
2024
Document type:
Article
Country of publication: