PMID- 33530496
OWN - NLM
STAT- MEDLINE
DCOM- 20210413
LR  - 20210413
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 3
DP  - 2021 Jan 26
TI  - Hypoxia-Induced S100A8 Expression Activates Microglial Inflammation and Promotes 
      Neuronal Apoptosis.
LID - 10.3390/ijms22031205 [doi]
LID - 1205
AB  - 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.
FAU - Ha, Ji Sun
AU  - Ha JS
AD  - Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, 
      Korea.
FAU - Choi, Hye-Rim
AU  - Choi HR
AD  - Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, 
      Korea.
FAU - Kim, In Sik
AU  - Kim IS
AD  - Department of Biomedical Laboratory Science, School of Medicine, Eulji 
      University, Uijeongbu 11759, Korea.
FAU - Kim, Eun-A
AU  - Kim EA
AD  - Department of Biochemistry and Molecular Biology, University of Ulsan College of 
      Medicine, Seoul 05505, Korea.
FAU - Cho, Sung-Woo
AU  - Cho SW
AD  - Department of Biochemistry and Molecular Biology, University of Ulsan College of 
      Medicine, Seoul 05505, Korea.
FAU - Yang, Seung-Ju
AU  - Yang SJ
AUID- ORCID: 0000-0001-9261-2749
AD  - Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, 
      Korea.
LA  - eng
GR  - 2018R1D1A3A03000692/Ministry of Education/
GR  - 2018R1A2B6001743/Ministry of Science and ICT, South Korea/
PT  - Journal Article
DEP - 20210126
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (Calgranulin A)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (S100a8 protein, mouse)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Biomarkers
MH  - Calgranulin A/*genetics/metabolism
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Disease Susceptibility
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - *Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Hypoxia/*genetics/*metabolism
MH  - Inflammation/etiology/metabolism/pathology
MH  - Inflammation Mediators/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Mice
MH  - Microglia/*metabolism
MH  - Neurons/*metabolism
MH  - Phosphorylation
PMC - PMC7866104
OTO - NOTNLM
OT  - COX-2
OT  - S100A8
OT  - hypoxia
OT  - inflammasome
OT  - microglia
OT  - neuronal apoptosis
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/02/04 06:00
MHDA- 2021/04/14 06:00
PMCR- 2021/01/26
CRDT- 2021/02/03 01:02
PHST- 2020/12/04 00:00 [received]
PHST- 2021/01/06 00:00 [revised]
PHST- 2021/01/18 00:00 [accepted]
PHST- 2021/02/03 01:02 [entrez]
PHST- 2021/02/04 06:00 [pubmed]
PHST- 2021/04/14 06:00 [medline]
PHST- 2021/01/26 00:00 [pmc-release]
AID - ijms22031205 [pii]
AID - ijms-22-01205 [pii]
AID - 10.3390/ijms22031205 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jan 26;22(3):1205. doi: 10.3390/ijms22031205.