title: Differential regulation of monocytic expression of leukotriene and lipoxin receptors.
abstract: BACKGROUND
  Lipoxygenase pathway yields both pro-inflammatory leukotrienes and pro-resolving lipoxins. The aim of the present study was to determine the effects of T-lymphocytes and pro-inflammatory stimuli on the expression levels of the lipoxin FPR2/ALX receptor, and the leukotriene BLT1 receptor in monocytes and macrophages, and to characterize LXA4-induced effects on pro-inflammatory mediators.
  
  
  METHODS
  Human macrophages were co-cultured with activated CD4(+) cells. THP-1 cells were stimulated with different cytokines, LXA4 and supernatant from activated CD4(+) cells. mRNA was extracted for qPCR experiments and protein was analyzed by flow cytometry.
  
  
  RESULTS
  Co-culture of macrophages with activated CD4(+) cells or their supernatants up-regulated macrophage FPR2/ALX expression but did not alter BLT1 receptor expression. Monocyte stimulation with IFN-γ up-regulated FPR2/ALX mRNA and protein levels, whereas BLT1 mRNA was down-regulated. Finally, LXA4 decreased mRNA levels of MMP-9, CXCL16, IL-1β, and IL-8 in THP-1 cells.
  
  
  CONCLUSIONS
  The present study shows that pro-inflammatory stimuli lead to FPR2/ALX expression. LXA4 induces an anti-inflammatory response, which could participate in the resolution of inflammation.
authors.affiliation: Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. Electronic address: marcelo.petri@ki.se.
authors.forename: Marcelo Heron
authors.initials: MH
authors.lastname: Petri
authors.affiliation: Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Silke
authors.initials: S
authors.lastname: Thul
authors.affiliation: Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: Ovchinnikova
authors.affiliation: Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Bäck
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000235:genetics*; D018102:Receptors, Leukotriene B4 / Q000235:genetics*; D044067:Receptors, Lipoxin / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C105101:FPR2 protein, human; C442142:HSH2D protein, human; C513240:LTB4R protein, human; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D018102:Receptors, Leukotriene B4; D044067:Receptors, Lipoxin; D007371:Interferon-gamma
keywords: Eicosanoids; Inflammation; Leukotriene; Lipoxin; Lipoxygenase; Monocyte; Resolution of inflammation