title: Phosphorylation of mitogen- and stress-activated protein kinase-1 in astrocytic inflammation: a possible role in inhibiting production of inflammatory cytokines.
abstract: OBJECTIVE
  It is generally accepted that inflammation has a role in the progression of many central nervous system (CNS) diseases, although the mechanisms through which this occurs remain unclear. Among mitogen-activated protein kinase (MAPK) targets, mitogen- and stress-activated protein kinase (MSK1) has been thought to be involved in the pathology of inflammatory gene expression. In this study, the roles of MSK1 activation in neuroinflammation were investigated.
  
  
  METHODS
  The bacterial lipopolysaccharide (LPS)-induced brain injury model was performed on Sprague-Dawley rats. The dynamic expression changes and the cellular location of p-MSK1 in the brain cortex were detected by Western blot and immunofluorescence staining. The synthesis of inflammatory cytokines in astrocytes was detected by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Phosphorylated MSK1 (p-MSK1 Thr-581) was induced significantly after intracerebral injection of LPS into the lateral ventricles of the rat brain. Specific upregulation of p-MSK1 in astrocytes was also observed in inflamed cerebral cortex. At 1 day after LPS stimulation, iNOS, TNFα expression, and the astrocyte marker glial fibrillary acidic protein (GFAP) were increased significantly. Also, in vitro studies indicated that the upregulation of p-MSK1 (Thr-581) may be involved in the subsequent astrocyte inflammatory process, following LPS challenge. Using an enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with LPS in primary astrocytes stimulated the synthesis of inflammatory cytokines, through MAPKs signaling pathways. In cultured primary astrocytes, both knock-down of total MSK1 by small interfering RNAs (siRNA) or specific mutation of Thr-581 resulted in higher production of certain cytokines, such as TNFα and IL-6.
  
  
  CONCLUSIONS
  Collectively, these results suggest that MSK1 phosphorylation is associated with the regulation of LPS-induced brain injury and possibly acts as a negative regulator of inflammation.
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Xide
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Lanchun
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Dekang
authors.initials: D
authors.lastname: Nie
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Comprehensive Surgical Laboratory, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, P.R.China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1