title: Dectin-1 and NOD2 mediate cathepsin activation in zymosan-induced arthritis in mice.
abstract: OBJECTIVE
  Activation of pattern recognition receptors (PRR) may contribute to arthritis. Here, we elucidated the role of NOD2, a genetic cause of inflammatory arthritis, and several other PRR in a murine model of inflammatory arthritis.
  
  
  METHODS
  The roles of CR3, TLR2, MyD88, NOD1, NOD2, Dectin-1 and Dectin-2 were tested in vivo in arthritis elicited by intra-articular injections of zymosan, the fungal cell wall components curdlan, laminarin and mannan, and the bacterial cell wall peptidoglycan.
  
  
  RESULTS
  Dectin-1, and to a lesser extent Dectin-2, contributed to arthritis. TLR2, MyD88 and CR3 played non-essential roles. Observations based on injection of curdlan, laminarin or mannan supported the dominant role of the Dectin-1 pathway in the joint. We demonstrated differential roles for NOD1 and NOD2 and identified NOD2 as a novel and essential mediator of zymosan-induced arthritis.
  
  
  CONCLUSIONS
  Together, Dectin-1 and NOD2 are critical, sentinel receptors in the arthritogenic effects of zymosan. Our data identify a novel role for NOD2 during inflammatory responses within joints.
authors.affiliation: Oregon Health and Science University, Mail stop: L467 AD, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA. rosenzwh@ohsu.edu
authors.forename: Holly L
authors.initials: HL
authors.lastname: Rosenzweig
authors.forename: Jenna S
authors.initials: JS
authors.lastname: Clowers
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nunez
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.forename: Michael P
authors.initials: MP
authors.lastname: Davey
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D002403:Cathepsins / Q000378:metabolism*; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007596:Joints / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism; D015054:Zymosan / Q000276:immunology*; D047071:beta-Glucans / Q000276:immunology; D000099181:Dectin-1
chemical_list: D002403:Cathepsins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053473:Nod2 Signaling Adaptor Protein; D051193:Toll-Like Receptors; D015054:Zymosan; D047071:beta-Glucans; D000099181:Dectin-1; C495945:Nod2 protein, mouse; C445340:dectin-2, mouse; C038459:curdlan