Lipocalin 2 is a regulator of macrophage polarization and NF-κB/STAT3 pathway activation

Hong Guo, Daozhong Jin, Xiaoli Chen

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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-κB), c-Jun, and STAT3 signaling pathways as well as an up-regualtion of expression of NF-κB and STAT3 target genes such as IL-1β, IL-6, iNOS, and MCP-1 in Lcn2-/- BMDMs compared with WT controls. Pre-treatment of recombinant Lcn2 attenuated LPS-stimulated degradation of IκBα and STAT3 phosphorylation as well as LPS-induced gene expression of IL-6 and iNOS in Lcn2-/- BMDMs. Moreover, the NFκB inhibitor markedly blocked LPS-stimulated STAT3 phosphorylation in Lcn2-/- BMDMs. These results together with the time course of Lcn2 secretion, NFκB 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 NFκBSTAT3 loop.

Original languageEnglish (US)
Pages (from-to)1616-1628
Number of pages13
JournalMolecular Endocrinology
Issue number10
StatePublished - Oct 1 2014

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© 2014 by the Endocrine Society. All rights reserved.


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