IL-17A exacerbates caspase-12-dependent neuronal apoptosis following ischemia through the Src-PLCγ-calpain pathway.
Exp Neurol
; 379: 114863, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38871070
ABSTRACT
Interleukin-17 A (IL-17 A) contributes to inflammation and causes secondary injury in post-stroke patients. However, little is known regarding the mechanisms that IL-17 A is implicated in the processes of neuronal death during ischemia. In this study, the mouse models of middle cerebral artery occlusion/reperfusion (MCAO/R)-induced ischemic stroke and oxygen-glucose deprivation/reoxygenation (OGD/R)-simulated in vitro ischemia in neurons were employed to explore the role of IL-17 A in promoting neuronal apoptosis. Mechanistically, endoplasmic reticulum stress (ERS)-induced neuronal apoptosis was accelerated by IL-17 A activation through the caspase-12-dependent pathway. Blocking calpain or phospholipase Cγ (PLCγ) inhibited IL-17 A-mediated neuronal apoptosis under ERS by inhibiting caspase-12 cleavage. Src and IL-17 A are linked, and PLCγ directly binds to activated Src. This binding causes intracellular Ca2+ flux and activates the calpain-caspase-12 cascade in neurons. The neurological scores showed that intracerebroventricular (ICV) injection of an IL-17 A neutralizing mAb decreased the severity of I/R-induced brain injury and suppressed apoptosis in MCAO mice. Our findings reveal that IL-17 A increases caspase-12-mediated neuronal apoptosis, and IL-17 A suppression may have therapeutic potential for ischemic stroke.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calpain
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Signal Transduction
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Brain Ischemia
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Apoptosis
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Interleukin-17
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Phospholipase C gamma
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Caspase 12
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Mice, Inbred C57BL
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Neurons
Limits:
Animals
Language:
En
Journal:
Exp Neurol
/
Exp. neurol
/
Experimental neurology
Year:
2024
Document type:
Article
Country of publication: