PMID- 25127375
OWN - NLM
STAT- MEDLINE
DCOM- 20150610
LR  - 20211021
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 28
IP  - 10
DP  - 2014 Oct
TI  - Lipocalin 2 is a regulator of macrophage polarization and NF-kappaB/STAT3 pathway 
      activation.
PG  - 1616-28
LID - 10.1210/me.2014-1092 [doi]
AB  - 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.
FAU - Guo, Hong
AU  - Guo H
AD  - Department of Food Science and Nutrition, University of Minnesota-Twin Cities, 
      Saint Paul, Minnesota 55108.
FAU - Jin, Daozhong
AU  - Jin D
FAU - Chen, Xiaoli
AU  - Chen X
LA  - eng
GR  - P30 DK050456/DK/NIDDK NIH HHS/United States
GR  - R01 DK080743/DK/NIDDK NIH HHS/United States
GR  - R01DK080743/DK/NIDDK NIH HHS/United States
GR  - 2P30DK050456/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140815
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (CD11c Antigen)
RN  - 0 (Lipocalin-2)
RN  - 0 (Lipocalins)
RN  - 0 (NF-kappa B)
RN  - 0 (Oncogene Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 126469-30-5 (Lcn2 protein, mouse)
RN  - EC 3.5.3.1 (Arg1 protein, mouse)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Acute-Phase Proteins/genetics/*metabolism
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Arginase/metabolism
MH  - CD11c Antigen/metabolism
MH  - Cell Polarity/*physiology
MH  - Diet, High-Fat
MH  - Inflammation/metabolism
MH  - Lipocalin-2
MH  - Lipocalins/genetics/*metabolism
MH  - Liver/metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/*metabolism
MH  - Obesity/metabolism
MH  - Oncogene Proteins/genetics/*metabolism
MH  - Phosphorylation
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction/*physiology
PMC - PMC4179633
EDAT- 2014/08/16 06:00
MHDA- 2015/06/11 06:00
PMCR- 2015/10/01
CRDT- 2014/08/16 06:00
PHST- 2014/08/16 06:00 [entrez]
PHST- 2014/08/16 06:00 [pubmed]
PHST- 2015/06/11 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - ME-14-1092 [pii]
AID - 10.1210/me.2014-1092 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2014 Oct;28(10):1616-28. doi: 10.1210/me.2014-1092. Epub 2014 Aug 
      15.