HSPA12B regulates SSeCKS-mediated astrocyte inflammatory activation in neuroinflammation.
Exp Cell Res
; 339(2): 310-9, 2015 Dec 10.
Article
em En
| MEDLINE
| ID: mdl-26428665
ABSTRACT
Reactive astrocytosis has been considered either beneficial or detrimental effection in neuroinflammatory disease. HSPA12B, a new member belongs to the 70-kDa family of heat shock proteins (HSP70) which could modulate inflammatory response, also shows an connection with the astrocyte activation. Recently, it was reported that Src-Suppressed-C Kinase Substrate (SSeCKS) was detected in heat shock protein A12B (HSPA12B) interacting proteins using a yeast 2-hybrid system. SSeCKS, a major Lipopolysaccharide (LPS) response protein, has been involved in regulating astrocyte activation via production of proinflammatory factor in CNS inflammation. In this study, we found HSPA12B might regulate the expression and activity of SSeCKS to promote astrocyte inflammatory activation and release of inflammatory mediators, such as TNF-α and IL-1ß in spinal cord primary astroglial cultures exposed to LPS treatment. The promoting mechanism of interaction between HSPA12B and SSeCKS on LPS-induced astrocyte activation was mediated via the activation of JNK and p38 signaling pathways but not ERK1/2 MAPK signaling pathway. HSPA12B binded to SSeCKS via its both N terminus consisted of amino acids 1-330 and C terminus consisted of amino acids 1278-1596. And, in vivo, we confirmed the interaction between HSPA12B and SSeCKS of astrocyte activation in the pathogenesis of EAE. The regulatory mechanisms of HSPA12B-SSeCKS interaction may possibly be the key therapeutic strategy of neuroinflammatory disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Astrócitos
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Proteínas de Choque Térmico HSP70
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Proteínas de Ciclo Celular
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Proteínas de Ancoragem à Quinase A
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Inflamação
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China