Neurochemical Research

, Volume 37, Issue 1, pp 5–14 | Cite as

Involvement of CLEC16A in Activation of Astrocytes After LPS Treated

  • Xinmin Wu
  • Jing Li
  • Chun Chen
  • Yaohua Yan
  • Shengyang Jiang
  • Xiaohong Wu
  • Bai Shao
  • Jin Xu
  • Lihua Kang
  • Yeqing Huang
  • Lin Zhu
  • Yuhong Ji
  • Yilu Gao
Original Paper


CLEC16A, C-type lectin domain family 16, member A was recently found to be associated with inflation process in the autoimmune diseases. In this study, we elucidated the dynamic expression changes and localization of CLEC16A in lipopolysaccharide (LPS)-induced neuroinflammatory processes in adult rats. CLEC16A expression was strongly induced in active astrocytes in inflamed cerebral cortex. In vitro studies indicated that the up-regulation of CLEC16A may be involved in the subsequent astrocyte activation following LPS challenge. And Knock-down of CLEC16A in cultured primary astrocytes by siRNA showed that CLEC16A was required for the activation of astrocytes induced by LPS. Collectively, these results suggested CLEC16A may be important in host defense in astrocyte-mediated immune response. Understanding the cell signal pathway may provide a novel strategy against inflammatory and immune reaction in neuroinflammtion in CNS.


CLEC16A Astrocytes Lipopolysaccharide Innate immune response Inflammatory 



C-type lectin domain family 16, member A


Tumor necrosis factor-alpha




Central nervous system


Polyacrylamide gel electrophoresis


Enhanced chemiluminescence system


Reverse transcriptase PCR


Glial fibrillary acidic protein


Neuronal nuclei


Proliferating cell nuclear antigen


Glyceraldehyde-3-phosphate dehydrogenase



This study was supported by the National Natural Science Foundation of China (No. 81070992) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Supplementary material

11064_2011_581_MOESM1_ESM.tif (7.2 mb)
Supplementary material 1 (TIFF 7,383 kb)


  1. 1.
    Paul AF, Anne-Marie W, Himali BF et al (2005) Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide. Blood 128:1649–1666Google Scholar
  2. 2.
    McGeer LP, Itagaki S et al (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285–1291PubMedGoogle Scholar
  3. 3.
    Liu B, Hong JS (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 304:1–7PubMedCrossRefGoogle Scholar
  4. 4.
    Rosi S, Ramirez-Amaya V, Vazdarjanova A, Worley PF et al (2005) Neuroinflammation alters the hippocampal pattern of behaviorally induced Arc expression. J Neurosci 25:723–731PubMedCrossRefGoogle Scholar
  5. 5.
    Ridet JL, Malhotra SK, Privat A et al (1997) Reactive astrocytes: cellularand molecular cues to biological function. Trends Neurosci 20:570–577PubMedCrossRefGoogle Scholar
  6. 6.
    Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626–640PubMedCrossRefGoogle Scholar
  7. 7.
    Mark AR, Gareth RJ, Xianyuan S et al (2005) The cytokine IL-1βactivates IFN response factor 3 in human fetal astrocytes in culture1. J Immunol 174:3719–3726Google Scholar
  8. 8.
    Eddleston M, Mucke L (1993) Molecular profile of reactive astrocytes–implications for their role in neurologic disease. J Neurosci 54:15CrossRefGoogle Scholar
  9. 9.
    Dong Y, Benveniste EN (2001) Immune function of astrocytes. Glia 36:180PubMedCrossRefGoogle Scholar
  10. 10.
    Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563–581PubMedCrossRefGoogle Scholar
  11. 11.
    Liu L, Rudin M, Kozlova EN (2000) Glial cell proliferation in the spinal cord after dorsal rhizotomy or sciatic nerve transection in the adult rat. Exp Brain Res 131:64–73PubMedCrossRefGoogle Scholar
  12. 12.
    Olivier N, Anna G, Cecily EH et al (2005) Activation of protease-activated receptor-1 triggers astrogliosis after brain injury. J Neurosci 25(17):4319–4329CrossRefGoogle Scholar
  13. 13.
    Carla C, Daniela D, Helgi BS et al (2007) Activation of melanocortin 4 receptors reduces the inflammatory response and prevents apoptosis induced by lipopolysaccharide and interferon-γ in astrocytes. Endocrinology 148(10):4918–4926CrossRefGoogle Scholar
  14. 14.
    Hakonarson H, Grant SF, Bradfield JP et al (2007) A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 448:591–594PubMedCrossRefGoogle Scholar
  15. 15.
    Consortium The Wellcome Trust Case Control (2007) Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 447:661–678CrossRefGoogle Scholar
  16. 16.
    Hafler DA, Compston A, Sawcer S et al (2007) Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 357:851–862PubMedCrossRefGoogle Scholar
  17. 17.
    John AT, Neil MW, Jason DC et al (2007) Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 39(7):857–864CrossRefGoogle Scholar
  18. 18.
    Shah VB, Huang YC, Keshwara R et al (2008) β-Glucan activates microglia without inducing cytokine production in Dectin-1-dependent manner. J Immunol 180:2777–2785PubMedGoogle Scholar
  19. 19.
    Aloisi F (2001) Immune function of microglia. Glia 36:165–179PubMedCrossRefGoogle Scholar
  20. 20.
    Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318PubMedCrossRefGoogle Scholar
  21. 21.
    Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28:138–145PubMedCrossRefGoogle Scholar
  22. 22.
    Jack CS, Arbour N, Manusow J et al (2005) TLR signaling tailors innate immune responses in human microglia and astrocytes1. J Immunol 175:4320–4330Google Scholar
  23. 23.
    Gehrmann J, Banati RB et al (1995) Amyloid precursor protein (APP) expression in multiple sclerosis lesions. Glia 15:141–151PubMedCrossRefGoogle Scholar
  24. 24.
    Sylvain N, Serge R (2000) Role of microglial-derived tumor necrosis factor in mediating CD14 transcription and nuclear factor k B activity in the brain during endotoxemia. J Neurosci 20(9):3456–3468Google Scholar
  25. 25.
    Stadlin A, Tsang D, MacDonall JS et al (1992) An in vitro study on increased neuronal and astrocytic vulnerability to neurotoxic injury after in utero cocaine exposure: the reversal effects of GM1 treatment. Prog Brain Res 94:339–350PubMedCrossRefGoogle Scholar
  26. 26.
    Morris GF, Mathews MB (1989) Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Chem 264:13856–13864PubMedGoogle Scholar
  27. 27.
    Geijtenbeek TBH, Sonja IG (2009) Signalling through C type lectin receptors: shaping immune responses. Nat Rev Immunol 7:465–479CrossRefGoogle Scholar
  28. 28.
    Zhao G, Flavin M (2000) Differential sensitivity of rat hippocampal and cortical astrocytes to oxygen-glucose deprivation injury. Neurosci Lett 285:177–180PubMedCrossRefGoogle Scholar
  29. 29.
    Smith SJ (1992) Do astrocytes process neural information? Prog Brain Res 94:119–136PubMedCrossRefGoogle Scholar
  30. 30.
    Mun˜ oz-Fernandez MA, Fresno M (1998) The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible nitric oxide synthase in the development and pathology of the nervous system. Prog Neurobiol 56:307–340CrossRefGoogle Scholar
  31. 31.
    Ana G, Sergio S, Vittorio G (2008) Endothelin-1 regulates astrocyte proliferation and reactive gliosis via a JNK/c-jun signaling pathway. J Neurosci 28(10):2394–2408CrossRefGoogle Scholar
  32. 32.
    David MU, Eddie R, Clifford AL et al (2005) Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood 106:2543–2550CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Xinmin Wu
    • 1
  • Jing Li
    • 1
    • 2
  • Chun Chen
    • 2
  • Yaohua Yan
    • 1
  • Shengyang Jiang
    • 2
  • Xiaohong Wu
    • 1
  • Bai Shao
    • 1
  • Jin Xu
    • 1
  • Lihua Kang
    • 2
  • Yeqing Huang
    • 2
  • Lin Zhu
    • 2
  • Yuhong Ji
    • 2
  • Yilu Gao
    • 1
  1. 1.Department of NeurosurgeryAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Department of Immunology, Medical CollegeNantong UniversityNantongPeople’s Republic of China

Personalised recommendations