2. Academic Validation
  3. Lipocalin-2 Is a chemokine inducer in the central nervous system: role of chemokine ligand 10 (CXCL10) in lipocalin-2-induced cell migration

Lipocalin-2 Is a chemokine inducer in the central nervous system: role of chemokine ligand 10 (CXCL10) in lipocalin-2-induced cell migration

  • J Biol Chem. 2011 Dec 23;286(51):43855-43870. doi: 10.1074/jbc.M111.299248.
Shinrye Lee 1,  Jong-Heon Kim 1,  Jae-Hong Kim 1,  Jung-Wan Seo 1,  Hyung-Soo Han 2,  Won-Ha Lee 3,  Kiyoshi Mori 4,  Kazuwa Nakao 4,  Jonathan Barasch 5,  Kyoungho Suk 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
  • 2 Department of Physiology, Brain Science & Engineering Institute, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
  • 3 Departments of School of Life Sciences and Biotechnology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
  • 4 Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
  • 5 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10027.
  • 6 Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Korea. Electronic address: ksuk@knu.ac.kr.
PMID: 22030398 DOI: 10.1074/jbc.M111.299248
Abstract

The secreted protein lipocalin-2 (LCN2) has been implicated in diverse cellular processes, including cell morphology and migration. Little is known, however, about the role of LCN2 in the CNS. Here, we show that LCN2 promotes cell migration through up-regulation of chemokines in brain. Studies using cultured glial cells, microvascular endothelial cells, and neuronal cells suggest that LCN2 may act as a chemokine inducer on the multiple cell types in the CNS. In particular, up-regulation of CXCL10 by JAK2/STAT3 and IKK/NF-κB pathways in astrocytes played a pivotal role in LCN2-induced cell migration. The cell migration-promoting activity of LCN2 in the CNS was verified in vivo using mouse models. The expression of LCN2 was notably increased in brain following LPS injection or focal injury. Mice lacking LCN2 showed the impaired migration of astrocytes to injury sites with a reduced CXCL10 expression in the neuroinflammation or injury models. Thus, the LCN2 proteins, secreted under inflammatory conditions, may amplify neuroinflammation by inducing CNS cells to secrete chemokines such as CXCL10, which recruit additional inflammatory cells.

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