PMID- 29115630
OWN - NLM
STAT- MEDLINE
DCOM- 20180716
LR  - 20181113
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 17
IP  - 1
DP  - 2018 Jan
TI  - TIPE2 governs macrophage polarization via negative regulation of mTORC1.
PG  - 952-960
LID - 10.3892/mmr.2017.7991 [doi]
AB  - Macrophages can be polarized into the inflammatory M1 lineage or the 
      immunomodulatory M2 lineage, depending on the differential tissue 
      microenvironment signaling, specific pathogens or cytokine stimulation. Tumor 
      necrosis factor alpha‑induced protein 8‑like protein 2 (TIPE2) has been demonstrated 
      to negatively regulate inflammation by inhibiting the Toll‑like receptor (TLR) 
      pathway. The present study utilized murine bone marrow derived macrophages 
      (BMDMs) as the model of undifferentiated (M0) macrophages to study the roles of 
      TIPE2 in the differential polarization status of BMDMs. It was observed that the 
      expression levels of TIPE2 were diminished in M1 macrophages treated with 
      lipopolysaccharide/interferon gamma, and elevated in M2 macrophages treated with 
      interleukin (IL)‑4. BMDMs with TIPE2 overexpression exhibited defective M1 
      polarization and enhanced responses to IL‑4 stimulation. TIPE2 impeded M1 
      polarization by interfering with mitogen‑activated protein kinase kinase kinase 
      7‑inhibitor of nuclear factor‑kappaB kinase subunit beta and B cell receptor‑associated 
      protein‑serine/threonine‑protein kinase mTOR complex 1 (mTORC1) activation. TIPE2 
      overexpression accelerated IL‑4 induced M2 polarization by dampening mTORC1 
      activation via the accelerated process of arginine to urea. Overall, these 
      results define a key role for TIPE2 in macrophage polarization by impeding mTORC1 
      response.
FAU - Jiang, Yuan
AU  - Jiang Y
AD  - Department of Pulmonology, Children's Hospital, Zhejiang University School of 
      Medicine, Hangzhou, Zhejiang 310051, P.R. China.
FAU - Li, Qiang
AU  - Li Q
AD  - Emergency Department, Second Affiliated Hospital of Zhejiang University School of 
      Medicine, Hangzhou, Zhejiang 310009, P.R. China.
FAU - Zhang, Yuanyuan
AU  - Zhang Y
AD  - Department of Pulmonology, Children's Hospital, Zhejiang University School of 
      Medicine, Hangzhou, Zhejiang 310051, P.R. China.
FAU - Gao, Yuzhi
AU  - Gao Y
AD  - Emergency Department, Second Affiliated Hospital of Zhejiang University School of 
      Medicine, Hangzhou, Zhejiang 310009, P.R. China.
FAU - Jiang, Libing
AU  - Jiang L
AD  - Emergency Department, Second Affiliated Hospital of Zhejiang University School of 
      Medicine, Hangzhou, Zhejiang 310009, P.R. China.
FAU - Chen, Zhimin
AU  - Chen Z
AD  - Department of Pulmonology, Children's Hospital, Zhejiang University School of 
      Medicine, Hangzhou, Zhejiang 310051, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20171106
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (TIPE2 protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP kinase kinase kinase 7)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Cytokines/metabolism
MH  - Gene Expression
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - MAP Kinase Kinase Kinases/metabolism
MH  - Macrophage Activation/*genetics/*immunology
MH  - Macrophages/*immunology/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 1/*metabolism
MH  - Mice
MH  - Protein Binding
PMC - PMC5780176
EDAT- 2017/11/09 06:00
MHDA- 2018/07/17 06:00
PMCR- 2017/11/06
CRDT- 2017/11/09 06:00
PHST- 2017/02/17 00:00 [received]
PHST- 2017/10/06 00:00 [accepted]
PHST- 2017/11/09 06:00 [pubmed]
PHST- 2018/07/17 06:00 [medline]
PHST- 2017/11/09 06:00 [entrez]
PHST- 2017/11/06 00:00 [pmc-release]
AID - mmr-17-01-0952 [pii]
AID - 10.3892/mmr.2017.7991 [doi]
PST - ppublish
SO  - Mol Med Rep. 2018 Jan;17(1):952-960. doi: 10.3892/mmr.2017.7991. Epub 2017 Nov 6.