PMID- 8600159
OWN - NLM
STAT- MEDLINE
DCOM- 19960502
LR  - 20131121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 166
IP  - 3
DP  - 1996 Mar
TI  - Tumor necrosis factor decreases thrombin receptor expression in endothelial 
      cells.
PG  - 561-7
AB  - We examined the effects of the proinflammatory cytokine, tumor necrosis 
      factor-alpha (TNF alpha) on the expression of proteolytically activated thrombin 
      receptor (PATR) in human umbilical vein endothelial cells (HUVEC). PATR mRNA and 
      protein levels were measured in confluent HUVEC monolayers after challenge with 
      TNF alpha. Northern analysis indicated that TNF alpha treatment resulted in 2- to 
      3-fold decrease in PATR mRNA in a time- and dose-dependent manner. PATR mRNA 
      level returned to the control level within 6 hr. The nuclear run-on assay 
      indicated that the decreased mRNA signal was due to reduction in the 
      transcription rate. Immunoblotting experiments indicated that the decrease in 
      expression of PATR protein followed in time the decrease in mRNA; the lowest 
      level of protein expression was achieved at 22 hr after TNF alpha treatment. PATR 
      protein returned to basal value within 40 hr after TNA alpha challenge. To assess 
      alterations in endothelial cell function after TNF alpha treatment, we measured 
      thrombin-induced increase in cytosolic Ca2+ ([Ca2+]i) and the cell shape change 
      (measured by decrease in electrical impedance of endothelial cell monolayer). In 
      HUVEC treated with TNF alpha (100 U/ml for 22 hr), the rise in [Ca2+]i after 
      thrombin challenge was approximately 2-fold less than in control thrombin-treated 
      cells. The decrease in electrical impedance of HUVEC monolayers in response to 
      thrombin after TNF alpha treatment was also significantly reduced. However, the 
      rise in [Ca2+]i in response to histamine was not altered by TNF alpha 
      pretreatment. In conclusion, TNF alpha exposure of endothelial cells decreased 
      both mRNA and protein expression of PATR, which explain the decreased activation 
      of thrombin generated signals after the TNF alpha exposure.
FAU - Yan, W
AU  - Yan W
AD  - Department of Pharmacology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, 
      Illinois 60612, USA.
FAU - Tiruppathi, C
AU  - Tiruppathi C
FAU - Qiao, R
AU  - Qiao R
FAU - Lum, H
AU  - Lum H
FAU - Malik, A B
AU  - Malik AB
LA  - eng
GR  - HL-07529/HL/NHLBI NIH HHS/United States
GR  - HL-27016/HL/NHLBI NIH HHS/United States
GR  - HL-45638/HL/NHLBI 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 Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Thrombin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.21.5 (Thrombin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Calcium/analysis
MH  - Cell Size
MH  - Cytosol/chemistry
MH  - Electric Impedance
MH  - Endothelium, Vascular/cytology/drug effects/*metabolism/physiology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Molecular Sequence Data
MH  - RNA, Messenger/metabolism
MH  - Receptors, Thrombin/*biosynthesis/genetics
MH  - Thrombin/pharmacology
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Umbilical Veins
EDAT- 1996/03/01 00:00
MHDA- 2000/06/20 09:00
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1996/03/01 00:00 [entrez]
AID - 10.1002/(SICI)1097-4652(199603)166:3<561::AID-JCP10>3.0.CO;2-A [pii]
AID - 10.1002/(SICI)1097-4652(199603)166:3<561::AID-JCP10>3.0.CO;2-A [doi]
PST - ppublish
SO  - J Cell Physiol. 1996 Mar;166(3):561-7. doi: 
      10.1002/(SICI)1097-4652(199603)166:3<561::AID-JCP10>3.0.CO;2-A.