| First Author | Jang E | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 3 | Pages | 1176-90 |
| PubMed ID | 23207546 | Mgi Jnum | J:196978 |
| Mgi Id | MGI:5490419 | Doi | 10.1096/fj.12-222257 |
| Citation | Jang E, et al. (2013) Secreted protein lipocalin-2 promotes microglial M1 polarization. FASEB J 27(3):1176-90 |
| abstractText | 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 1 mug/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. |
