title: Pro-inflammatory cytokine and caspase-1 responses to pattern recognition receptor activation of neutrophils and dendritic cells in Behcet's disease.
abstract: OBJECTIVE
  Activated innate immunity is implicated in the pathogenesis of Behcet's disease (BD). To clarify the mechanisms of innate immune responses, we investigated inflammasome activation in dendritic cells (DCs) and neutrophils, following stimulation with two different pattern recognition receptors (PRRs) RIG-1-like (RLR) and NOD-like (NLR) in patients with BD.
  
  
  METHODS
  Sixteen active BD patients with mucocutaneous lesions and 17 healthy controls (HCs) were included in this study. DCs were generated from monocytes. DCs and isolated neutrophils were activated by RLR and NLR ligands. Caspase-1 activation and expression of p38 and RIP2 were determined by flow cytometry. Levels of IL-1β, IL-6, TNF-α, IFN-α and IL-18 in culture supernatants were measured by ELISA.
  
  
  RESULTS
  Activation of caspase-1 following intracellular PRR stimulation was found to be of similar levels in DCs and neutrophils of BD patients compared with HCs. However, activation of DCs from BD patients to NOD2 stimulus measured by the expression of RIP2 and p38 as well as IL-18 levels was found to be slightly defective (P < 0.05). In neutrophil cultures, IL-6 levels were lower in response to all stimuli in patients with BD compared with HCs (P < 0.01).
  
  
  CONCLUSIONS
  Inflammasome formation following stimulation with NOD1/NOD2 and RIG measured by caspase-1 activation, cytokine levels and expression of RIP2 and p38 seems to be functionally normal in DCs and neutrophils of BD patients, although slightly defective responses in some pathways and cytokine levels were observed. These results may suggest that caspase-1-independent pathways such as toll-like receptors may be more prominent in BD pathogenesis.
authors: Department of Immunology, Marmara University, School of Medicine, Istanbul, Turkey.
authors: Filiz
authors: F
authors: Türe-Özdemir
authors: Aysin
authors: A
authors: Tulunay
authors: Mehmet Onur
authors: MO
authors: Elbasi
authors: Imren
authors: I
authors: Tatli
authors: Anne-Marie
authors: AM
authors: Maurer
authors: Gonca
authors: G
authors: Mumcu
authors: Haner
authors: H
authors: Direskeneli
authors: Emel
authors: E
authors: Eksioglu-Demiralp
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000276:immunology* / Q000503:physiopathology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D020170:Caspase 1 / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism; D012016:Reference Values; D018709:Statistics, Nonparametric; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D020170:Caspase 1; D016207:Cytokines; D015850:Interleukin-6; D051192:Receptors, Pattern Recognition; D018168:Receptors, Retinoic Acid; D000099176:Noggin Protein; C437968:PLAAT4 protein, human