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Hypoxia-Induced S100A8 Expression Activates Microglial Inflammation and Promotes Neuronal Apoptosis

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Abstract
S100 calcium-binding protein A8 (S100A8), a danger-associated molecular pattern, has emerged as an important mediator of the pro-inflammatory response. Some S100 proteins play a prominent role in neuroinflammatory disorders and increase the secretion of pro-inflammatory cytokines in microglial cells. The aim of this study was to determine whether S100A8 induced neuronal apoptosis during cerebral hypoxia and elucidate its mechanism of action. In this study, we reported that the S100A8 protein expression was increased in mouse neuronal and microglial cells when exposed to hypoxia, and induced neuroinflammation and neuronal apoptosis. S100A8, secreted from neurons under hypoxia, activated the secretion of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) through phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in microglia. Also, phosphorylation of ERK via the TLR4 receptor induced the priming of the NLRP3 inflammasome. The changes in Cyclooxygenase-2 (COX-2) expression, a well-known inflammatory activator, were regulated by the S100A8 expression in microglial cells. Knockdown of S100A8 levels by using shRNA revealed that microglial S100A8 expression activated COX-2 expression, leading to neuronal apoptosis under hypoxia. These results suggested that S100A8 may be an important molecule for bidirectional microglia-neuron communication and a new therapeutic target for neurological disorders caused by microglial inflammation during hypoxia.
Author(s)
하지선최혜림김인식김은아조성우양승주
Issued Date
2021
Type
Article
Keyword
S100A8microgliainflammasomehypoxianeuronal apoptosisCOX-2
DOI
10.3390/ijms22031205
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7766
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_6bc149efe3bf4347a7ab4b63d2b63c5e&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Hypoxia-Induced%20S100A8%20Expression%20Activates%20Microglial%20Inflammation%20and%20Promotes%20Neuronal%20Apoptosis&offset=0&pcAvailability=true
Publisher
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Location
스위스
Language
영어
ISSN
1422-0067
Citation Volume
22
Citation Number
3
Citation Start Page
1205
Citation End Page
1205
Appears in Collections:
Medicine > Medicine
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