PMID- 10753909
OWN - NLM
STAT- MEDLINE
DCOM- 20000505
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 15
DP  - 2000 Apr 14
TI  - Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 
      (TLR-4) in cultured human dermal endothelial cells. Differential expression of 
      TLR-4 and TLR-2 in endothelial cells.
PG  - 11058-63
AB  - A missense mutation in the cytoplasmic domain of the Toll-like receptor-4 (TLR-4) 
      has been identified as the defect responsible for lipopolysaccharide (LPS) 
      hyporesponsiveness in C3H/HeJ mice. TLR-4 and TLR-2 have recently been implicated 
      in LPS signaling in studies where these receptors were overexpressed in LPS 
      non-responsive 293 human embryonic kidney cells. However, the signaling role of 
      TLR-4 or TLR-2 in human cells with natural LPS response remains largely 
      undefined. Here we show that human dermal microvessel endothelial cells (HMEC) 
      and human umbilical vein endothelial cells express predominantly TLR-4 but very 
      weak TLR-2 and respond vigorously to LPS but not to Mycobacterium tuberculosis 
      19-kDa lipoprotein. Transient transfection of non-signaling mutant forms of TLR-4 
      and anti-TLR-4 monoclonal antibody inhibited LPS-induced NF-kappaB activation in 
      HMEC, while a monoclonal antibody against TLR-2 was ineffective. In contrast to 
      LPS responsiveness, the ability of HMEC to respond to 19-kDa lipoprotein 
      correlated with the expression of TLR-2. Transfection of TLR-2 into HMEC 
      conferred responsiveness to 19-kDa lipoprotein. These data indicate that TLR-4 is 
      the LPS signaling receptor in HMEC and that human endothelial cells (EC) express 
      predominantly TLR-4 and weak TLR-2, which may explain why they do not respond to 
      19-kDa lipoprotein. The differential expression of TLRs on human EC may have 
      important implications in the participation of vascular EC in innate immune 
      defense mechanisms against various infectious pathogens, which may use different 
      TLRs to signal.
FAU - Faure, E
AU  - Faure E
AD  - Division of Pediatric Infectious Diseases, Ahmanson Department of Pediatrics, 
      Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center and UCLA 
      School of Medicine, Los Angeles, California 90048, USA.
FAU - Equils, O
AU  - Equils O
FAU - Sieling, P A
AU  - Sieling PA
FAU - Thomas, L
AU  - Thomas L
FAU - Zhang, F X
AU  - Zhang FX
FAU - Kirschning, C J
AU  - Kirschning CJ
FAU - Polentarutti, N
AU  - Polentarutti N
FAU - Muzio, M
AU  - Muzio M
FAU - Arditi, M
AU  - Arditi M
LA  - eng
GR  - AI40275/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Drosophila Proteins
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - Humans
MH  - Lipopolysaccharide Receptors/pharmacology
MH  - Lipopolysaccharides/*pharmacology
MH  - Membrane Glycoproteins/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - NF-kappa B/*metabolism
MH  - Receptors, Cell Surface/*physiology
MH  - Skin/cytology
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
EDAT- 2001/02/07 11:00
MHDA- 2001/02/07 11:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/02/07 11:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - S0021-9258(19)80948-1 [pii]
AID - 10.1074/jbc.275.15.11058 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Apr 14;275(15):11058-63. doi: 10.1074/jbc.275.15.11058.