PMID- 34471375
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220426
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 14
DP  - 2021
TI  - Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage 
      Properties.
PG  - 4189-4203
LID - 10.2147/JIR.S328916 [doi]
AB  - PURPOSE: Lipocalin-2 (Lcn2) is an acute-phase protein and elevated in several 
      inflammatory diseases. This study aimed to determine whether Lcn2 alleviates 
      inflammation and explore the underlying cellular mechanisms. METHODS: C57BL/6 
      Lcn2-deficient (Lcn2(-/-)) male mice were intraperitoneally injected with 
      lipopolysaccharide (LPS) to build systemic inflammation model. The inflammatory 
      processes were investigated. The morphology of villi was measured by scanning 
      electron microscopy (SEM). The levels of inflammatory factors were detected by 
      ELISA and qPCR analysis. The production of Lcn2 was determined with 
      immunofluorescence staining by confocal microscope. The molecular mechanism of 
      Lcn2 in bone marrow-derived macrophages (BMDMs) was analyzed by mass spectrometry 
      (MS)-based quantitative proteomic analysis. RESULTS: Compared to wild-type (WT) 
      mice injected with LPS, Lcn2(-/-) mice injected with LPS showed increased 
      inflammatory damage in jejunum and ileum, and significantly elevated the levels 
      of multiple pro-inflammatory cytokines. After determining that Lcn2 was mainly 
      located in the cytoplasm of macrophages, we isolated BMDMs from Lcn2(-/-) mice to 
      evaluate their function. During LPS challenge, transcripts of pro-inflammatory 
      cytokines were all significantly increased in BMDMs from Lcn2(-/-) mice, while 
      those of anti-inflammatory cytokines were significantly decreased when compared 
      with the cytokines in BMDMs from WT mice. A label-free relative quantitation 
      proteomics analysis showed that LPS-treated BMDMs from Lcn2(-/-) mice had 
      elevated levels of pro-inflammatory pathways, but reduced phagocytosis and 
      autophagy when compared with LPS-treated BMDMs from WT mice. CONCLUSION: These 
      findings demonstrated that Lcn2 was a potent protective factor in response to 
      systemic inflammation and might be an indispensable factor for macrophage 
      functions.
CI  - (c) 2021 Du et al.
FAU - Du, Huahua
AU  - Du H
AD  - MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, 
      Zhejiang University, Zhejiang, 310058, People's Republic of China.
FAU - Liang, Li
AU  - Liang L
AD  - MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, 
      Zhejiang University, Zhejiang, 310058, People's Republic of China.
FAU - Li, Jiahui
AU  - Li J
AD  - MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, 
      Zhejiang University, Zhejiang, 310058, People's Republic of China.
FAU - Xiong, Qingqing
AU  - Xiong Q
AD  - MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, 
      Zhejiang University, Zhejiang, 310058, People's Republic of China.
FAU - Yu, Xin
AU  - Yu X
AD  - Department of Anesthesia, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang 
      University, Zhejiang, 310016, People's Republic of China.
FAU - Yu, Hong
AU  - Yu H
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Zhejiang, 310016, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210826
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC8405166
OTO - NOTNLM
OT  - BMDMs
OT  - Lcn2
OT  - macrophages
OT  - systemic inflammation
COIS- The authors report no conflicts of interest in this work.
EDAT- 2021/09/03 06:00
MHDA- 2021/09/03 06:01
PMCR- 2021/08/26
CRDT- 2021/09/02 06:53
PHST- 2021/07/11 00:00 [received]
PHST- 2021/08/13 00:00 [accepted]
PHST- 2021/09/02 06:53 [entrez]
PHST- 2021/09/03 06:00 [pubmed]
PHST- 2021/09/03 06:01 [medline]
PHST- 2021/08/26 00:00 [pmc-release]
AID - 328916 [pii]
AID - 10.2147/JIR.S328916 [doi]
PST - epublish
SO  - J Inflamm Res. 2021 Aug 26;14:4189-4203. doi: 10.2147/JIR.S328916. eCollection 
      2021.