PMID- 29284516
OWN - NLM
STAT- MEDLINE
DCOM- 20181102
LR  - 20181113
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Dec 29
TI  - Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation 
      of Ly6C(+) macrophages.
PG  - 217
LID - 10.1186/s12931-017-0707-6 [doi]
LID - 217
AB  - BACKGROUND: SOCS3 (suppressor of cytokine signaling 3) is a negative regulator of 
      JAK/STAT3 signaling pathway and participates in the regulation of lung 
      inflammation in a mouse model with acute lung injury (ALI). However, it is not 
      well understood how SOCS3 regulates lung inflammation in the ALI mouse model. 
      METHOD: In the present study, we investigated the effects of SOCS3 on modulation 
      of Ly6C(+) monocyte phenotypes in a mouse model with lipopolysaccharide 
      (LPS)-induced ALI. Conditional SOCS3(Lyz2cre) mice with myeloid cell-restricted 
      depletion of SOCS3 gene were created by breeding transgenic Lyz2Cre mice with 
      SOCS3(fl/fl) mice. Wilde-type (WT) and SOCS3(Lyz2cre) mice were intratracheal 
      instilled with 5 mg/kg LPS for 2 days. Lung, bronchoalveolar lavage (BAL) and 
      blood were collected for analysis by flow cytometry, ELISA, qRT-PCR and Western 
      blot analysis. RESULTS: The studies in the ALI mouse model revealed that myeloid 
      cell-restricted SOCS3 deficiency exacerbated the severity of ALI as compared to 
      the WT mice. The increased severity of ALI in SOCS3-deficient mice was associated 
      with higher populations of neutrophils, T lymphocytes and Ly6C(+) monocytes in 
      the inflamed lung tissues. In addition, CCR2 and CXCL15 were elevated, and 
      accompanied by greater expression and activation of STAT3 in the lung of 
      SOCS3-deficient mice. SOCS3-deficient bone marrow-derived macrophages (BMDMs) 
      expressed a higher amount of TNF-alpha, and adoptive transfer of the 
      SOCS3-deficient Ly6C(+) BMDMs into WT mice enhanced the severity of ALI than 
      adoptive transfer of WT control BMDMs. However, depletion of Ly6C(+) circulating 
      monocytes by anti-Ly6C(+) neutralizing antibody moderately attenuated neutrophil 
      infiltration and resulted in lower prevalence of Ly6C(+) cells in the lung of 
      treated mice. CONCLUSION: Myeloid cell-restricted lack of SOCS3 induced more 
      severe ALI through modulation of Ly6C(+) subtype macrophages. The results provide 
      insight into a new role of SOCS3 in modulation of Ly6C(+) monocyte phenotypes and 
      provide a novel therapeutic strategy for ALI by molecular intervention of 
      macrophages subtypes.
FAU - Jiang, Zhilong
AU  - Jiang Z
FAU - Chen, Zhihong
AU  - Chen Z
FAU - Li, Liyang
AU  - Li L
FAU - Zhou, Wenjun
AU  - Zhou W
FAU - Zhu, Lei
AU  - Zhu L
AD  - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng 
      Lin Road, Shanghai, 200032, China. zhu.lei@zs-hospital.sh.cn.
LA  - eng
GR  - A654116001/Zhongshan Hospital, Fudan University in China/International
GR  - 81270078 and 81470211/National Natural Science Foundation of China/International
GR  - 81270137 and 81300054/National Natural Science Foundation of China/International
GR  - 15GWZK0102/Shanghai three-year plan of the key subject construction in public 
      health-infectious diseases and pathogenic microorganism/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171229
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Antigens, Ly)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Ly-6C antigen, mouse)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
SB  - IM
MH  - Acute Lung Injury/*chemically induced/immunology/*metabolism
MH  - Animals
MH  - Antigens, Ly/immunology/*metabolism
MH  - Cells, Cultured
MH  - Lipopolysaccharides/*toxicity
MH  - Macrophages/drug effects/immunology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Suppressor of Cytokine Signaling 3 Protein/*deficiency/immunology
PMC - PMC5747159
OTO - NOTNLM
OT  - Acute lung injury
OT  - JAK/STAT3 signaling
OT  - Ly6C(+) macrophages
OT  - SOCS3
COIS- ETHICS APPROVAL: All animal protocols were reviewed and approved by the 
      laboratory animal care and use committee of Zhongshan Hospital, Fudan University. 
      CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The funders had no 
      role in study design, data collection and analysis, decision to publish, or 
      preparation of the manuscript. None of the authors affiliated with this 
      manuscript have any commercial or associations that might pose a conflict 
      interest. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to 
      jurisdictional claims in published maps and institutional affiliations.
EDAT- 2017/12/30 06:00
MHDA- 2018/11/06 06:00
PMCR- 2017/12/29
CRDT- 2017/12/30 06:00
PHST- 2017/10/07 00:00 [received]
PHST- 2017/12/18 00:00 [accepted]
PHST- 2017/12/30 06:00 [entrez]
PHST- 2017/12/30 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2017/12/29 00:00 [pmc-release]
AID - 10.1186/s12931-017-0707-6 [pii]
AID - 707 [pii]
AID - 10.1186/s12931-017-0707-6 [doi]
PST - epublish
SO  - Respir Res. 2017 Dec 29;18(1):217. doi: 10.1186/s12931-017-0707-6.