PMID- 10364168
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 25
DP  - 1999 Jun 18
TI  - Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by
      toll-like receptor 2.
PG  - 17406-9
AB  - The life-threatening complications of sepsis in humans are elicited by infection 
      with Gram-negative as well as Gram-positive bacteria. Recently,
      lipopolysaccharide (LPS), a major biologically active agent of Gram-negative
      bacteria, was shown to mediate cellular activation by a member of the human
      Toll-like receptor family, Toll-like receptor (TLR) 2. Here we investigate the
      mechanism of cellular activation by soluble peptidoglycan (sPGN) and lipoteichoic
      acid (LTA), main stimulatory components of Gram-positive bacteria. Like LPS, sPGN
      and LTA bind to the glycosylphosphatidylinositol-anchored membrane protein CD14
      and induce activation of the transcription factor NF-kappaB in host cells like
      macrophages. We show that whole Gram-positive bacteria, sPGN and LTA induce the
      activation of NF-kappaB in HEK293 cells expressing TLR2 but not in cells
      expressing TLR1 or TLR4. The sPGN- and LTA-induced NF-kappaB activation was not
      inhibited by polymyxin B, an antibiotic that binds and neutralizes LPS.
      Coexpression together with membrane CD14 enhances sPGN signal transmission
      through TLR2. In contrast to LPS signaling, activation of TLR2 by sPGN and LTA
      does not require serum. These findings identify TLR2 as a signal transducer for
      sPGN and LTA in addition to LPS.
FAU - Schwandner, R
AU  - Schwandner R
AD  - Tularik Inc., South San Francisco, California 94080, USA.
FAU - Dziarski, R
AU  - Dziarski R
FAU - Wesche, H
AU  - Wesche H
FAU - Rothe, M
AU  - Rothe M
FAU - Kirschning, C J
AU  - Kirschning CJ
LA  - eng
GR  - AI28797/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Drosophila Proteins)
RN  - 0 (Glycosylphosphatidylinositols)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptidoglycan)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Teichoic Acids)
RN  - 0 (Toll-Like Receptor 1)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 56411-57-5 (lipoteichoic acid)
RN  - J2VZ07J96K (Polymyxin B)
SB  - IM
MH  - Cell Line
MH  - *Drosophila Proteins
MH  - Glycosylphosphatidylinositols/metabolism
MH  - Gram-Negative Bacteria/metabolism
MH  - Gram-Positive Bacteria/metabolism
MH  - Humans
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Membrane Glycoproteins/*metabolism
MH  - NF-kappa B/metabolism
MH  - Peptidoglycan/*pharmacology
MH  - Polymyxin B/pharmacology
MH  - Receptors, Cell Surface/*metabolism
MH  - Signal Transduction
MH  - Teichoic Acids/*pharmacology
MH  - Toll-Like Receptor 1
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - Transcriptional Activation
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1074/jbc.274.25.17406 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 18;274(25):17406-9. doi: 10.1074/jbc.274.25.17406.