PMID- 16624877
OWN - NLM
STAT- MEDLINE
DCOM- 20060705
LR  - 20211020
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 103
IP  - 18
DP  - 2006 May 2
TI  - Differential induction of BLT receptor expression on human endothelial cells by 
      lipopolysaccharide, cytokines, and leukotriene B4.
PG  - 6913-8
AB  - Leukotriene (LT) B4 is a powerful chemotactic and immune modulating agent that 
      signals via two receptors denoted BLT1 and BLT2. Here we report that BLT1 and 
      BLT2 are expressed at low levels in an apparently silent state in human umbilical 
      vein endothelial cells (HUVEC). However, treatment with LPS leads to a >10 fold 
      increase in the levels of BLT1 mRNA without any significant effects on BLT2 mRNA. 
      In parallel, LPS also increases the amounts of BLT1 protein. Tumor necrosis 
      factor-alpha (TNF-alpha) increases the expression of BLT2 mRNA approximately 6 
      times above basal levels with only a modest increase in BLT1 mRNA. 
      Interleukin-1beta causes variable and parallel increases of both BLT1 and BLT2 
      mRNA. The natural ligand LTB4 also increases BLT1, but not BLT2, mRNA and protein 
      expression. Along with the induction of BLT1 and/or BLT2, HUVEC acquire the 
      capacity to respond to LTB4 with increased levels of intracellular calcium and 
      these signals can be blocked by isotype selective BLT antagonists, CP-105696 and 
      LY-255283. In addition, treatment of HUVEC with LTB4 causes increased release of 
      both nitrite, presumably reflecting nitric oxide (NO), and monocyte 
      chemoattractant protein-1. Our data indicate that expression of functional BLT 
      receptors may occur at the surface of endothelial cells in response to LPS, 
      cytokines, and ligand, which in turn may have functional consequences during the 
      early vascular responses to inflammation. Moreover, the results point to BLT 
      receptors as potential targets for pharmacological intervention in LT-dependent 
      inflammatory diseases such as asthma, rheumatoid arthritis, and arteriosclerosis.
FAU - Qiu, Hong
AU  - Qiu H
AD  - Department of Medical Biochemistry and Biophysics, Division of Chemistry II, 
      Karolinska Institutet, S-171 77 Stockholm, Sweden.
FAU - Johansson, Anne-Sofie
AU  - Johansson AS
FAU - Sjostrom, Mattias
AU  - Sjostrom M
FAU - Wan, Min
AU  - Wan M
FAU - Schroder, Oliver
AU  - Schroder O
FAU - Palmblad, Jan
AU  - Palmblad J
FAU - Haeggstrom, Jesper Z
AU  - Haeggstrom JZ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060419
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (LTB4R protein, human)
RN  - 0 (LTB4R2 protein, human)
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrites)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Leukotriene B4)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Tetrazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - H037W1I5AL (LY 255283)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Endothelial Cells/cytology/*metabolism
MH  - Humans
MH  - Interleukin-1/*metabolism
MH  - Leukotriene Antagonists/metabolism
MH  - Leukotriene B4/*metabolism
MH  - Lipopolysaccharides/*metabolism
MH  - Nitrites/metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - Receptors, Leukotriene B4/genetics/*metabolism
MH  - Receptors, Purinergic P2/genetics/*metabolism
MH  - Signal Transduction/physiology
MH  - Tetrazoles/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC1440767
COIS- Conflict of interest statement: No conflicts declared.
EDAT- 2006/04/21 09:00
MHDA- 2006/07/06 09:00
PMCR- 2006/05/02
CRDT- 2006/04/21 09:00
PHST- 2006/04/21 09:00 [pubmed]
PHST- 2006/07/06 09:00 [medline]
PHST- 2006/04/21 09:00 [entrez]
PHST- 2006/05/02 00:00 [pmc-release]
AID - 0602208103 [pii]
AID - 2065 [pii]
AID - 10.1073/pnas.0602208103 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2006 May 2;103(18):6913-8. doi: 
      10.1073/pnas.0602208103. Epub 2006 Apr 19.