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Apoptosis Signal-regulating Kinase 1 Silencing on Astroglial Inflammasomes in an Experimental Model of Ischemic Stroke

 So Yeong Cheon  ;  Eun Jung Kim  ;  So Yeon Kim  ;  Jeong Min Kim  ;  Eun Hee Kam  ;  Jong-Kwang Park  ;  Bon-Nyeo Koo 
 NEUROSCIENCE, Vol.390 : 218-230, 2018 
Journal Title
Issue Date
apoptosis signal-regulating kinase 1 ; astrocyte ; inflammasomes ; inflammatory response ; ischemic stroke
Activation of the inflammasome complex contributes to the inflammatory response and cell death under pathologic conditions. The nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 2 (NLRP2) inflammasome is activated in astrocytes after cerebral ischemia, which can aggravate ischemic damage. Apoptosis signal-regulating kinase 1 (ASK1) is an early activator and immune-regulator after ischemic injury, that can lead to cell death. The objective of the present study was to evaluate the role of ASK1 in controlling NLRP2 inflammasomes in astrocytes after cerebral ischemia. In a mouse model of ischemic stroke, the levels of NLRP2 inflammasome components, and interleukin (IL)-1β and IL-18, were quantified in different brain regions. In addition, an astrocyte cell line was subjected to oxygen-glucose deprivation and reperfusion (OGD/R) injury, and the levels of NLRP2 inflammasome factors, IL-1β and IL-18 were evaluated. Ischemic brain injury activated astrocytes. The levels of NLRP2 inflammasome components, IL-1β and IL-18 productions, and cell death increased in the cortex and striatum after ischemic injury. In cultured astrocytes, NLRP2 inflammasome components, IL-1β and IL-18 levels were upregulated after OGD/R. ASK1 silencing or inhibition efficiently reduced NLRP2 inflammasome components and pro-inflammatory cytokine levels in mice and cultured astrocytes. Our findings identify a key role for ASK1 in regulating astroglial inflammasomes after cerebral ischemia. We suggest ASK1 as one of the main targets for astroglial inflammasomes in ischemic stroke.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Koo, Bon-Nyeo(구본녀) ORCID logo https://orcid.org/0000-0002-3189-1673
Kim, So Yeon(김소연) ORCID logo https://orcid.org/0000-0001-5352-157X
Kim, Eun Jung(김은정) ORCID logo https://orcid.org/0000-0002-5693-1336
Kim, Jeongmin(김정민) ORCID logo https://orcid.org/0000-0002-0468-8012
Park, Jong-Kwang(박종광) ORCID logo https://orcid.org/0000-0002-7304-3509
Cheon, So Yeong(전소영)
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