title: Effects of diesel exhaust particles on macrophage polarization.
abstract: BACKGROUND
  Exposure to diesel exhaust particles (DEP) has long been associated with increased cardiovascular morbidity and mortality. The development of DEP toxicity seems to be linked to inflammation in which macrophages play a critical role. Macrophages can be polarized into proinflammatory M1 or anti-inflammatory M2 macrophages. The aim of this study was to identify the role of inflammation in DEP-induced toxicity by assessing the effects of DEP on macrophage polarization.
  
  
  METHODS
  Monocyte-derived macrophages (Mϕ) were stimulated with interferon γ and lipopolysaccharide or interleukin (IL)-4 to obtain M1 and M2 subtypes, respectively. To test the polarization capacity of DEP, Mϕ cells were exposed to DEP and compared to Mϕ, M1, and M2. We also studied the effects of DEP on already-polarized M1 or M2. The M1 markers assessed were tumor necrosis factor α (TNF-α) and IL-1β, while the M2 markers were the mannose receptor C type 1 (MRC-1) and transglutaminase 2 (TGM2).
  
  
  RESULTS
  Western blots revealed a 31 kDa band corresponding to pro-IL-1β, but only in M1-polarized macrophages. In M1, we also observed an upregulation of TNF-α messenger RNA (mRNA) expression. MRC-1 and TGM2 mRNA expression were only significantly enhanced in M2. DEP had no effect on any of the M1/M2 markers assessed. Moreover, DEP were not able to modify the phenotype of already-polarized M1 or M2.
  
  
  CONCLUSIONS
  Mϕ incubation with DEP did not have any effect on macrophage polarization, at least on the markers assessed in this study, namely, TNF-α/IL-1β for M1, and MRC-1/TGM2 for M2. Hence, these data argue against an important role of inflammation in DEP-induced vascular toxicity.
authors.affiliation: 1 Laboratory of Physiology and Pharmacology, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Labranche
authors.affiliation: 1 Laboratory of Physiology and Pharmacology, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: C El
authors.initials: CE
authors.lastname: Khattabi
authors.affiliation: 2 Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Berkenboom
authors.affiliation: 1 Laboratory of Physiology and Pharmacology, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Pochet
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C573543:MRC1 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D007371:Interferon-gamma
keywords: Diesel exhaust particles; inflammation; macrophage polarization