PMID- 30073169
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 5
DP  - 2018
TI  - LPS Induces mTORC1 and mTORC2 Activation During Monocyte Adhesion.
PG  - 67
LID - 10.3389/fmolb.2018.00067 [doi]
LID - 67
AB  - Monocyte adhesion is a crucial step in transmigration and can be induced by 
      lipopolysaccharide (LPS). Here, we studied the role of mammalian target of 
      rapamycin (mTOR) complexes, mTORC1 and mTORC2, and PKC in this process. We used 
      THP-1 cells, a human monocytic cell line, to investigate monocyte adhesion under 
      static and flow conditions. We observed that 1.0 mug/mL LPS increased PI3K/mTORC2 
      pathway and PKC activity after 1 h of incubation. WYE-354 10(-6) M (mTORC2/mTORC1 
      inhibitor) and 10(-6) M wortmannin avoided monocyte adhesion in culture plates. 
      In addition, WYE also blocked LPS-induced CD11a expression. Interestingly, 
      rapamycin and WYE-354 blocked both LPS-induced monocyte adhesion in a cell 
      monolayer and actin cytoskeleton rearrangement, confirming mTORC1 involvement in 
      this process. Once activated, PKC activates mTORC1/S6K pathway in a similar 
      effect observed to LPS. Activation of the mTORC1/S6K pathway was attenuated by 
      10(-6) M U0126, an MEK/ERK inhibitor, and 10(-6) M calphostin C, a PKC inhibitor, 
      indicating that the MEK/ERK/TSC2 axis acts as a mediator. In agreement, 80 nM PMA 
      (a PKC activator) mimicked the effect of LPS on the activation of the 
      MEK/ERK/TSC2/mTORC1/S6K pathway, monocyte adhesion to ECV cells and actin 
      cytoskeleton rearrangement. Our findings show that LPS induces activation of mTOR 
      complexes. This signaling pathway led to integrin expression and cytoskeleton 
      rearrangement resulting in monocyte adhesion. These results describe a new 
      molecular mechanism involved in monocyte adhesion in immune-based diseases.
FAU - Ribeiro, Marcelle C
AU  - Ribeiro MC
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Peruchetti, Diogo B
AU  - Peruchetti DB
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Silva, Leandro S
AU  - Silva LS
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Silva-Filho, Joao L
AU  - Silva-Filho JL
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Souza, Mariana C
AU  - Souza MC
AD  - Fundacao Oswaldo Cruz, Instituto de Tecnologia em Farmacos, Rio de Janeiro, 
      Brazil.
FAU - Henriques, Maria das Gracas
AU  - Henriques MDG
AD  - Fundacao Oswaldo Cruz, Instituto de Tecnologia em Farmacos, Rio de Janeiro, 
      Brazil.
FAU - Caruso-Neves, Celso
AU  - Caruso-Neves C
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
AD  - Instituto Nacional de Ciencia e Tecnologia em Medicina Regenerativa, Rio de 
      Janeiro, Brazil.
FAU - Pinheiro, Ana Acacia S
AU  - Pinheiro AAS
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20180718
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC6058081
OTO - NOTNLM
OT  - adhesion
OT  - human acute monocytic leukemia cell line
OT  - lipopolysaccharide
OT  - mTORC1
OT  - mTORC2
OT  - monocyte
OT  - phorbol ester
OT  - protein kinase C
EDAT- 2018/08/04 06:00
MHDA- 2018/08/04 06:01
PMCR- 2018/01/01
CRDT- 2018/08/04 06:00
PHST- 2017/11/01 00:00 [received]
PHST- 2018/06/28 00:00 [accepted]
PHST- 2018/08/04 06:00 [entrez]
PHST- 2018/08/04 06:00 [pubmed]
PHST- 2018/08/04 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fmolb.2018.00067 [doi]
PST - epublish
SO  - Front Mol Biosci. 2018 Jul 18;5:67. doi: 10.3389/fmolb.2018.00067. eCollection 
      2018.