PMID- 18924132
OWN - NLM
STAT- MEDLINE
DCOM- 20090106
LR  - 20211203
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 38
IP  - 11
DP  - 2008 Nov
TI  - Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate 
      immune cells.
PG  - 2981-92
LID - 10.1002/eji.200838761 [doi]
AB  - The mammalian target of rapamycin (mTOR) can be viewed as cellular master complex 
      scoring cellular vitality and stress. Whether mTOR controls also innate 
      immune-defenses is currently unknown. Here we demonstrate that TLR activate mTOR 
      via phosphoinositide 3-kinase/Akt. mTOR physically associates with the MyD88 
      scaffold protein to allow activation of interferon regulatory factor-5 and 
      interferon regulatory factor-7, known as master transcription factors for 
      pro-inflammatory cytokine- and type I IFN-genes. Unexpectedly, inactivation of 
      mTOR did not prevent but increased lethality of endotoxin-mediated shock, which 
      correlated with increased levels of IL-1beta. Mechanistically, mTOR suppresses 
      caspase-1 activation, thus inhibits release of bioactive IL-1beta. We have 
      identified mTOR as indispensable component of PRR signal pathways, which 
      orchestrates the defense program of innate immune cells.
FAU - Schmitz, Frank
AU  - Schmitz F
AD  - Institut fuer Medizinische Mikrobiologie, Immunologie und Hygiene, Technische 
      Universitaet Muenchen, Muenchen, Germany.
FAU - Heit, Antje
AU  - Heit A
FAU - Dreher, Stefan
AU  - Dreher S
FAU - Eisenacher, Katharina
AU  - Eisenacher K
FAU - Mages, Jorg
AU  - Mages J
FAU - Haas, Tobias
AU  - Haas T
FAU - Krug, Anne
AU  - Krug A
FAU - Janssen, Klaus-Peter
AU  - Janssen KP
FAU - Kirschning, Carsten J
AU  - Kirschning CJ
FAU - Wagner, Hermann
AU  - Wagner H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Cytokines)
RN  - 0 (Interferon Regulatory Factor-7)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Caspase 1/physiology
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Humans
MH  - *Immunity, Innate
MH  - Interferon Regulatory Factor-7/physiology
MH  - Interleukin-1beta/biosynthesis
MH  - Lipopolysaccharides/toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Kinases/*physiology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Toll-Like Receptors/physiology
MH  - Transcription, Genetic
EDAT- 2008/10/17 09:00
MHDA- 2009/01/07 09:00
CRDT- 2008/10/17 09:00
PHST- 2008/10/17 09:00 [pubmed]
PHST- 2009/01/07 09:00 [medline]
PHST- 2008/10/17 09:00 [entrez]
AID - 10.1002/eji.200838761 [doi]
PST - ppublish
SO  - Eur J Immunol. 2008 Nov;38(11):2981-92. doi: 10.1002/eji.200838761.