PMID- 28273403
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20220310
IS  - 1365-3083 (Electronic)
IS  - 0300-9475 (Linking)
VI  - 85
IP  - 6
DP  - 2017 Jun
TI  - PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice.
PG  - 395-405
LID - 10.1111/sji.12545 [doi]
AB  - Macrophages play an important role in the pathogenesis of COPD. Macrophage 
      polarization towards the M2 phenotype has been observed in the lung tissues of 
      COPD patients and cigarette smokers. The molecular basis of this process remains 
      unclear, and it has not been completely illuminated in animal models of 
      emphysema. In our study, we combined cigarette smoke (CS) exposure with 
      intraperitoneal injection of cigarette smoke extract (CSE) to build an emphysema 
      model. We found by immunohistochemical staining and flow cytometry that the 
      expression level of CD206 and the ratio of M2 to M1 macrophages was increased in 
      emphysematous mice. We also demonstrated that decreased protein level for 
      phosphatase and tensin homology deleted on chromosome ten (PTEN) and increased 
      total protein levels for phosphorylation -protein kinase B (p-AKT) in the lung 
      tissue of emphysematous mice and in CSE-treated RAW264.7 cells. In both bone 
      marrow-derived macrophages (BMDMs) from emphysematous mice and CSE-treated 
      RAW264.7 cells, we observed by RT-PCR that the mRNA levels of M2 
      macrophage-related markers and cytokines were increased. Furthermore, M1 
      macrophage-related markers and cytokines were decreased. Meanwhile we treated 
      BMDMs from emphysematous mice and CSE-treated RAW264.7 cells with the 
      phosphoinositide 3-kinase (PI3K)/Akt inhibitor (LY294002), we observed a 
      reduction in RNA levels of M2 macrophage-related markers and cytokines. In 
      conclusion, we confirmed that macrophage M2 polarization was induced in 
      emphysematous mice generated by CS exposure combined with intraperitoneal 
      injection of CSE. We also showed that M2 polarization was mediated through 
      PTEN/PI3k/AKT pathway activation.
CI  - (c) 2017 The Foundation for the Scandinavian Journal of Immunology.
FAU - Lu, J
AU  - Lu J
AD  - Department of Respiratory Medicine, the Third XiangYa Hospital of Central South 
      University, Changsha, Hunan Province, China.
FAU - Xie, L
AU  - Xie L
AD  - Department of Respiratory Medicine, the Third XiangYa Hospital of Central South 
      University, Changsha, Hunan Province, China.
FAU - Liu, C
AU  - Liu C
AD  - Department of Respiratory Medicine, the Third XiangYa Hospital of Central South 
      University, Changsha, Hunan Province, China.
FAU - Zhang, Q
AU  - Zhang Q
AD  - Department of Respiratory Medicine, the Third XiangYa Hospital of Central South 
      University, Changsha, Hunan Province, China.
FAU - Sun, S
AU  - Sun S
AUID- ORCID: 0000-0002-9705-4632
AD  - Department of Respiratory Medicine, the Third XiangYa Hospital of Central South 
      University, Changsha, Hunan Province, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Cytokines)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Smoke)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - Cytokines/genetics/metabolism
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - Injections, Intraperitoneal
MH  - Lectins, C-Type/metabolism
MH  - Lung/drug effects/metabolism/pathology
MH  - Macrophage Activation
MH  - Macrophages/classification/*metabolism
MH  - Male
MH  - Mannose Receptor
MH  - Mannose-Binding Lectins/metabolism
MH  - Mice, Inbred C57BL
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Pulmonary Emphysema/chemically induced/*metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Smoke
MH  - Tobacco Products/toxicity
EDAT- 2017/03/09 06:00
MHDA- 2017/08/02 06:00
CRDT- 2017/03/09 06:00
PHST- 2016/12/19 00:00 [received]
PHST- 2017/03/02 00:00 [accepted]
PHST- 2017/03/09 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2017/03/09 06:00 [entrez]
AID - 10.1111/sji.12545 [doi]
PST - ppublish
SO  - Scand J Immunol. 2017 Jun;85(6):395-405. doi: 10.1111/sji.12545.