Pro- and anti-inflammatory substances modulate expression of the leukotriene B4 receptor, BLT1, in human monocytes.
The high-affinity leukotriene B(4) (LTB(4)) 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 LTB(4). 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.
Pettersson
Annika
A
Division of Molecular Neurobiology, Wallenberg Neuroscience Center, Lund University, Sweden.
Sabirsh
Alan
A
Bristulf
Jesper
J
Kidd-Ljunggren
Karin
K
Ljungberg
Bengt
B
Owman
Christer
C
Karlsson
Ulf
U
D002633:Chemotaxis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000235:genetics / Q000378:metabolism*; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D018836:Inflammation Mediators; C513240:LTB4R protein, human; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003907:Dexamethasone; D007371:Interferon-gamma