title: HSPA12B regulates SSeCKS-mediated astrocyte inflammatory activation in neuroinflammation.
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-1β 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.
authors.affiliation: Surgical Comprehensive Laboratory and Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Surgical Comprehensive Laboratory and Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Da-Min
authors.initials: DM
authors.lastname: Yuan
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Shen
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Surgical Comprehensive Laboratory and Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Lu
authors.affiliation: Surgical Comprehensive Laboratory and Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Guo
authors.affiliation: Surgical Comprehensive Laboratory and Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Surgical Comprehensive Laboratory and Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China. Electronic address: Chenjian_NT@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Geriatrics, Nanjing Second Hospital Affiliated to Nanjing Medical University, 121 Jiangjiayuan, Nanjing 210011, China. Electronic address: luxiang_ny@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006168:Guinea Pigs; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D018797:Cell Cycle Proteins; D018840:HSP70 Heat-Shock Proteins; C472131:HSPA12B protein, human; D008070:Lipopolysaccharides
keywords: Astrocyte activation; HSPA12B; MAPK; Neuroinflammation; SSeCKS