Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1204740 on February 23, 2005

Published online before print February 23, 2005
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(Journal of Leukocyte Biology. 2005;77:1018-1025.)
© 2005 by Society for Leukocyte Biology

Pro- and anti-inflammatory substances modulate expression of the leukotriene B4 receptor, BLT1, in human monocytes

Annika Pettersson*, Alan Sabirsh{dagger}, Jesper Bristulf*, Karin Kidd-Ljunggren{ddagger}, Bengt Ljungberg{ddagger}, Christer Owman* and Ulf Karlsson*,{ddagger},1

* Division of Molecular Neurobiology, Wallenberg Neuroscience Center, Lund University, and
{ddagger} Division of Infectious Diseases, Lund University Hospital, Sweden; and
{dagger} Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

1Correspondence: Division of Molecular Neurobiology, Wallenberg Neuroscience Center, BMC A12, Lund University, 22184 Lund, Sweden. E-mail: Ulf.Karlsson{at}mphy.lu.se

The high-affinity leukotriene B4 (LTB4) receptor, BLT1, is a chemotactic receptor involved in inflammatory responses. In this study, we have explored the regulation of BLT1 expression in human monocytes by pro- and anti-inflammatory cytokines, lipopolysaccharide (LPS), and dexamethasone. We found that proinflammatory mediators, such as interferon-{gamma} (IFN-{gamma}), tumor necrosis factor-{alpha}, and LPS, down-regulated expression, whereas the anti-inflammatory cytokine, interleukin-10, and dexamethasone up-regulated BLT1 mRNA expression. The effect of IFN-{gamma} on BLT1 mRNA expression was rapidly detectable (<4 h) and concentration-dependent (1–50 ng/ml) and seems to be exerted through a block in transcriptional activity. Alterations in mRNA expression were accompanied by changes in BLT1 surface expression, and receptor down-modulation following IFN-{gamma} stimulation resulted in a diminished chemotactic response to LTB4. The regulation of BLT1 mRNA and receptor protein expression was similar to the regulation of the monocyte chemoattractant protein-1 chemokine receptor, CC chemokine recptor 2 (CCR2). Flow cytometric analysis of fresh peripheral blood cells revealed that classical (CD14++CD16) monocytes express high levels of BLT1 and CCR2 and that both receptors are down-regulated on CD14+CD16+ monocytes. Apart from providing insight into the regulation of BLT1 in human monocytes, our results reveal a parallel expression and regulation of BLT1 and CCR2, which may help to understand monocyte trafficking during pathophysiological conditions.

Key Words: mononuclear phagocytes • LTB4 • IFN-{gamma} • inflammatory mediators




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