<P>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 t...
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https://www.riss.kr/link?id=A107671905
2013
-
SCOPUS,SCIE
학술저널
1176-1190(15쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P>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 t...
<P>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<SUB>50</SUB> 1 μg/ml), but not glutathione <I>S</I>-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.</P>