Lipocalin-2 Is a chemokine inducer in the central nervous system: role of chemokine ligand 10 (CXCL10) in lipocalin-2-induced cell migration.
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.
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
Shinrye
S
Lee
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
Jong-Heon
JH
Kim
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
Jae-Hong
JH
Kim
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
Jung-Wan
JW
Seo
Department of Physiology, Brain Science & Engineering Institute, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
Hyung-Soo
HS
Han
Departments of School of Life Sciences and Biotechnology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
Won-Ha
WH
Lee
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Kiyoshi
K
Mori
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Kazuwa
K
Nakao
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10027.
Jonathan
J
Barasch
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Korea. Electronic address: ksuk@knu.ac.kr.
Kyoungho
K
Suk
D000209:Acute-Phase Proteins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000378:metabolism; D002465:Cell Movement; D054357:Chemokine CXCL10 / Q000737:chemistry*; D018925:Chemokines / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D000071068:Lipocalin-2; D054834:Lipocalins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D050796:STAT3 Transcription Factor / Q000378:metabolism
D000209:Acute-Phase Proteins; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D017077:Culture Media, Conditioned; C485433:Cxcl10 protein, mouse; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C071332:Lcn2 protein, mouse