Regulation of inflammatory transcription factors by heat shock protein 70 in primary cultured astrocytes exposed to oxygen-glucose deprivation

J. Y. Kim, M. A. Yenari, Jongeun Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Inflammation is an important event in ischemic injury. These immune responses begin with the expression of pro-inflammatory genes modulating transcription factors, such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and signal transducers and activator of transcription-1 (STAT-1). The 70-kDa heat shock protein (Hsp70) can both induce and arrest inflammatory reactions and lead to improved neurological outcome in experimental brain injury and ischemia. Since Hsp70 are induced under heat stress, we investigated the link between Hsp70 neuroprotection and phosphorylation of inhibitor of κB (IκB), c-Jun N-terminal kinases (JNK) and p38 through co-immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) assay. Transcription factors and pro-inflammatory genes were quantified by immunoblotting, electrophoretic-mobility shift assay and reverse transcription-polymerase chain reaction assays. The results showed that heat stress led to Hsp70 overexpression which rendered neuroprotection after ischemia-like injury. Overexpression Hsp70 also interrupts the phosphorylation of IκB, JNK and p38 and blunts DNA binding of their transcription factors (NF-κB, AP-1 and STAT-1), effectively downregulating the expression of pro-inflammatory genes in heat-pretreated astrocytes. Taken together, these results suggest that overexpression of Hsp70 may protect against brain ischemia via an anti-inflammatory mechanism by interrupting the phosphorylation of upstream of transcription factors.

Original languageEnglish
Pages (from-to)272-280
Number of pages9
JournalNeuroscience
Volume286
DOIs
Publication statusPublished - 2015 Feb 2

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HSP70 Heat-Shock Proteins
Astrocytes
Transcription Factors
STAT1 Transcription Factor
Oxygen
Glucose
Hot Temperature
Transcription Factor AP-1
Phosphorylation
Brain Ischemia
Genes
JNK Mitogen-Activated Protein Kinases
Wounds and Injuries
Electrophoretic Mobility Shift Assay
Immunoprecipitation
Immunoblotting
Brain Injuries
Reverse Transcription
Anti-Inflammatory Agents
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Medicine(all)

Cite this

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abstract = "Inflammation is an important event in ischemic injury. These immune responses begin with the expression of pro-inflammatory genes modulating transcription factors, such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and signal transducers and activator of transcription-1 (STAT-1). The 70-kDa heat shock protein (Hsp70) can both induce and arrest inflammatory reactions and lead to improved neurological outcome in experimental brain injury and ischemia. Since Hsp70 are induced under heat stress, we investigated the link between Hsp70 neuroprotection and phosphorylation of inhibitor of κB (IκB), c-Jun N-terminal kinases (JNK) and p38 through co-immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) assay. Transcription factors and pro-inflammatory genes were quantified by immunoblotting, electrophoretic-mobility shift assay and reverse transcription-polymerase chain reaction assays. The results showed that heat stress led to Hsp70 overexpression which rendered neuroprotection after ischemia-like injury. Overexpression Hsp70 also interrupts the phosphorylation of IκB, JNK and p38 and blunts DNA binding of their transcription factors (NF-κB, AP-1 and STAT-1), effectively downregulating the expression of pro-inflammatory genes in heat-pretreated astrocytes. Taken together, these results suggest that overexpression of Hsp70 may protect against brain ischemia via an anti-inflammatory mechanism by interrupting the phosphorylation of upstream of transcription factors.",
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Regulation of inflammatory transcription factors by heat shock protein 70 in primary cultured astrocytes exposed to oxygen-glucose deprivation. / Kim, J. Y.; Yenari, M. A.; Lee, Jongeun.

In: Neuroscience, Vol. 286, 02.02.2015, p. 272-280.

Research output: Contribution to journalArticle

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