PMID- 35606692
OWN - NLM
STAT- MEDLINE
DCOM- 20220525
LR  - 20220716
IS  - 1471-2172 (Electronic)
IS  - 1471-2172 (Linking)
VI  - 23
IP  - 1
DP  - 2022 May 23
TI  - Lack of STAT6 enhances murine acute lung injury through NLRP3/p38 MAPK signaling 
      pathway in macrophages.
PG  - 25
LID - 10.1186/s12865-022-00500-9 [doi]
LID - 25
AB  - BACKGROUND: Signal transducer and activator of transcription 6 (STAT6) is an 
      intracelluar transcriotion factor and NLRP3 (Nod-like receptor containing a pyrin 
      domain 3) is a component of NLRP3 inflammasome in pyroptotic cells. There was 
      increased activation of STAT6 and expression of NLRP3 in mice with murine acute 
      lung injury (ALI). However, it is unknown their roles in the development of 
      murine ALI. We in this study, investigated the effects of STAT6 signaling on 
      murine ALI and pyroptosis in STAT6 knock-out (KO) mice and macrophages. RESULTS: 
      STAT6 was activated in the lung tissues of mice 2 days after intratracheal 
      treatmemt with 5 mg/kg LPS. Lack of STAT6 expression in KO mice induced more 
      severe lung inflammation, associated with elevated neutrophil influx and 
      expression of TNF-alpha, IL-6 and IL-1beta in the inflamed lung tissues. In 
      addition, the expression of NLRP3, ASC (apoptosis-associated speck-like protein 
      containing a CARD), p-p38 MAPK (p38 mitogen-activated protein kinase) and ratio 
      of LC3-II/I (microtubule-associated protein-1 light chain-3) was increased, 
      accompanied with the increased polarization of Siglec-F(-) subtype macrophages in 
      KO mice with ALI. Further studies in bone marrow-derived macrophages (BMDMs) 
      revealed that lack of STAT6 increased the expression of NLRP3 and p-p38 MAPK, in 
      association with elevated expression of TNF-alpha, IL-1beta and Calreticulin in 
      LPS-treated KO BMDMs. CONCLUSIONS: Lack of STAT6 exacerbated murine ALI through 
      improving the expression of NLRP3 and activation of p38 MAPK in macrophages. 
      STAT6 has an immune suppressive role in the development of ALI and would be a 
      promising therapeutic target in the treatment of ALI and possibly among patients 
      with acute respiratory distress syndrome (ARDS).
CI  - (c) 2022. The Author(s).
FAU - Hu, Lu
AU  - Hu L
AD  - Department of Pulmonary Medicine, Zhongshan Hospital Fudan University, 180 Feng 
      Lin Road, Shanghai, 200032, China.
AD  - Department of Respiratory, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'An, China.
FAU - Shao, Changzhou
AU  - Shao C
AD  - Department of Pulmonary Medicine, Zhongshan Hospital Fudan University, 180 Feng 
      Lin Road, Shanghai, 200032, China.
FAU - Pan, Linyue
AU  - Pan L
AD  - Department of Pulmonary Medicine, Zhongshan Hospital Fudan University, 180 Feng 
      Lin Road, Shanghai, 200032, China.
FAU - Jiang, Zhilong
AU  - Jiang Z
AD  - Department of Pulmonary Medicine, Zhongshan Hospital Fudan University, 180 Feng 
      Lin Road, Shanghai, 200032, China. jiang.zhilong@zs-hospital.sh.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220523
PL  - England
TA  - BMC Immunol
JT  - BMC immunology
JID - 100966980
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
RN  - 0 (Stat6 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - *Acute Lung Injury/drug therapy/metabolism
MH  - Animals
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
MH  - STAT6 Transcription Factor/genetics/metabolism/pharmacology
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC9126100
OTO - NOTNLM
OT  - Acute lung injury
OT  - Cytokines
OT  - Macrophages
OT  - Pyroptosis
OT  - STAT6
COIS- The authors declare no competing interests.
EDAT- 2022/05/24 06:00
MHDA- 2022/05/26 06:00
PMCR- 2022/05/23
CRDT- 2022/05/23 23:43
PHST- 2021/08/11 00:00 [received]
PHST- 2022/05/09 00:00 [accepted]
PHST- 2022/05/23 23:43 [entrez]
PHST- 2022/05/24 06:00 [pubmed]
PHST- 2022/05/26 06:00 [medline]
PHST- 2022/05/23 00:00 [pmc-release]
AID - 10.1186/s12865-022-00500-9 [pii]
AID - 500 [pii]
AID - 10.1186/s12865-022-00500-9 [doi]
PST - epublish
SO  - BMC Immunol. 2022 May 23;23(1):25. doi: 10.1186/s12865-022-00500-9.