PMID- 11699072
OWN - NLM
STAT- MEDLINE
DCOM- 20020403
LR  - 20190916
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 16
IP  - 5
DP  - 2001 Nov
TI  - Human coronary endothelial cell activation by endotoxin is characterized by 
      NF-kappa B activation and TNF-alpha synthesis.
PG  - 349-54
AB  - Tumor necrosis factor-alpha (TNF-alpha), an early inflammatory mediator typically 
      regulated by nuclear factor kappa B (NF-kappa B), plays a critical role in the 
      development of cardiovascular dysfunction in sepsis. While several myocardial 
      cell types synthesize TNF-alpha, the importance of the myocardial endothelium in 
      sepsis-related cardiac cytokine production is unclear. To determine the role of 
      the human coronary artery endothelial cell (HCA-EC) in the cytokine response to 
      endotoxin we measured in vitro TNF-alpha synthesis, TNF-alpha mRNA, and the 
      associated NF-kappa B response to LPS. To determine the magnitude of the HCA-EC 
      response we assessed the TNF-alpha and NF-kappa B response to LPS in a human 
      monocytic cell line (THP-1) as well. We observed an increase in supernatant 
      TNF-alpha from LPS-stimulated HCA-EC (12 h) that was ablated by the proteosome 
      inhibitor, ALLN (N-acetyl-Leu-Leu-norleucinal). Similarly, ALLN-sensitive 
      TNF-alpha was produced by monocytes following LPS, although at concentrations 
      100-fold higher than HCA-EC. TNF-alpha mRNA from HCA-EC was detected at 60 min in 
      LPS-stimulated cells, but not in unstimulated cells or cells pretreated with 
      ALLN. NF-kappa B p50/p65 subunits were detectable in endothelial nuclear protein 
      60 min following LPS. In contrast, NF-kappa B subunits from monocytes were 
      detected at 15 min. Also, while ALLN only attenuated endothelial NF-kappa B 
      translocation, monocyte NF-kappa B translocation was completely inhibited. These 
      data suggest endotoxin-stimulated human coronary endothelial cells express 
      TNF-alpha, which is regulated in part by NF-kappa B activation, in a manner and 
      degree distinct from human monocytes.
FAU - Chan, E L
AU  - Chan EL
AD  - Department of Surgery, University of Texas Southwestern Medical Center, 5323 
      Harry Hines Boulevard, Dallas, Texas 75390-9158, USA.
FAU - Haudek, S B
AU  - Haudek SB
FAU - Giroir, B P
AU  - Giroir BP
FAU - Murphy, J T
AU  - Murphy JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Endotoxins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cells, Cultured
MH  - Coronary Vessels/*physiology
MH  - Cytosol/drug effects/metabolism
MH  - Endothelium, Vascular/drug effects/*physiology
MH  - Endotoxins/*toxicity
MH  - Humans
MH  - Kinetics
MH  - Lipopolysaccharides/toxicity
MH  - NF-kappa B/*metabolism
MH  - Transcription, Genetic/*drug effects
MH  - Tumor Necrosis Factor-alpha/biosynthesis/*genetics/metabolism
EDAT- 2001/11/09 10:00
MHDA- 2002/04/04 10:01
CRDT- 2001/11/09 10:00
PHST- 2001/11/09 10:00 [pubmed]
PHST- 2002/04/04 10:01 [medline]
PHST- 2001/11/09 10:00 [entrez]
AID - 10.1097/00024382-200116050-00005 [doi]
PST - ppublish
SO  - Shock. 2001 Nov;16(5):349-54. doi: 10.1097/00024382-200116050-00005.