| First Author | Guo H | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 10 | Pages | 1616-28 |
| PubMed ID | 25127375 | Mgi Jnum | J:216305 |
| Mgi Id | MGI:5608624 | Doi | 10.1210/me.2014-1092 |
| Citation | Guo H, et al. (2014) Lipocalin 2 is a regulator of macrophage polarization and NF-kappaB/STAT3 pathway activation. Mol Endocrinol 28(10):1616-28 |
| abstractText | Lipocalin 2 (Lcn2) has been previously characterized as an adipokine/cytokine and implicated in obesity and inflammation. Herein, we investigated the role and potential mechanism of Lcn2 in the regulation of macrophage polarization in obesity-associated inflammation. We observed that Lcn2-/- mice displayed an up-regulation of expression of M1 macrophage marker Cd11c but a down-regulation of M2 marker arginase 1 in adipose tissue and liver of mice upon a high-fat diet feeding. Lcn2-deficient bone marrow-derived macrophages (BMDMs) were more sensitive to lipopolysaccharide (LPS) stimulation, leading to a more profound up-regulation of expression of pro-inflammatory markers than wild-type (WT) BMDMs. Accordingly, LPS stimulation elicited an increase in the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), c-Jun, and STAT3 signaling pathways as well as an up-regualtion of expression of NF-kappaB and STAT3 target genes such as IL-1beta, IL-6, iNOS, and MCP-1 in Lcn2-/- BMDMs compared with WT controls. Pre-treatment of recombinant Lcn2 attenuated LPS-stimulated degradation of IkappaBalpha and STAT3 phosphorylation as well as LPS-induced gene expression of IL-6 and iNOS in Lcn2-/- BMDMs. Moreover, the NFkappaB inhibitor markedly blocked LPS-stimulated STAT3 phosphorylation in Lcn2-/- BMDMs. These results together with the time course of Lcn2 secretion, NFkappaB and STAT3 phosphorylation in response to LPS stimulation, suggest that Lcn2 plays a role as an anti-inflammatory regulator in macrophage activation via modulating a feed-forward activation of NFkappaB-STAT3 loop. |
