| Secreted protein lipocalin-2 promotes microglial M1 polarization. | |
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MedLine Citation:
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PMID: 23207546 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Activated macrophages are classified into two different forms: classically activated (M1) or alternatively activated (M2) macrophages. The presence of M1/M2 phenotypic polarization has also been suggested for microglia. Here, we report that the secreted protein lipocalin 2 (LCN2) amplifies M1 polarization of activated microglia. LCN2 protein (EC(50) 1 μg/ml), but not glutathione S-transferase used as a control, increased the M1-related gene expression in cultured mouse microglial cells after 8-24 h. LCN2 was secreted from M1-polarized, but not M2-polarized, microglia. LCN2 inhibited phosphorylation of STAT6 in IL-4-stimulated microglia, suggesting LCN2 suppression of the canonical M2 signaling. In the lipopolysaccharide (LPS)-induced mouse neuroinflammation model, the expression of LCN2 was notably increased in microglia. Primary microglial cultures derived from LCN2-deficient mice showed a suppressed M1 response and enhanced M2 response. Mice lacking LCN2 showed a markedly reduced M1-related gene expression in microglia after LPS injection, which was consistent with the results of histological analysis. Neuroinflammation-associated impairment in motor behavior and cognitive function was also attenuated in the LCN2-deficient mice, as determined by the rotarod performance test, fatigue test, open-field test, and object recognition task. These findings suggest that LCN2 is an M1-amplifier in brain microglial cells.-Jang, E., Lee, S., Kim, J.-H., Kim, J.-H., Seo, J.-W., Lee, W.-H., Mori, K., Nakao, K., Suk, K. Secreted protein lipocalin-2 promotes microglial M1 polarization. |
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Authors:
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Eunha Jang; Shinrye Lee; Jong-Heon Kim; Jae-Hong Kim; Jung-Wan Seo; Won-Ha Lee; Kiyoshi Mori; Kazuwa Nakao; Kyoungho Suk |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-4 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: - ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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*Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, and. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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