TY - JOUR
T1 - Dectin-1 and NOD2 mediate cathepsin activation in zymosan-induced arthritis in mice
AU - Rosenzweig, Holly L.
AU - Clowers, Jenna S.
AU - Nunez, Gabriel
AU - Rosenbaum, James T.
AU - Davey, Michael P.
N1 - Funding Information:
Acknowledgments We would like to thank Dr. Shizuo Akira (Osaka University, Japan) for the provision of the MyD88 KO mice, and our collaborators, Drs. Steve Planck and Tammy Martin, for their critical discussions. This work was supported by the US Department of Veterans Affairs Merit Review grant, National Eye Institute grant EY019020 along with support from the Gerlinger Award, the Stan and Madelle Rosenfeld Family Trust, and the William C. Kuzell Foundation. HLR also receives support from the American College of Rheumatology and Research to Prevent Blindness.
PY - 2011/7
Y1 - 2011/7
N2 - 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 nonessential 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.
AB - 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 nonessential 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.
KW - Arthritis models
KW - In vivo inflammation
KW - Innate immunity
KW - NOD2
KW - Zymosan
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U2 - 10.1007/s00011-011-0324-7
DO - 10.1007/s00011-011-0324-7
M3 - Article
C2 - 21424514
AN - SCOPUS:80051666900
SN - 1023-3830
VL - 60
SP - 705
EP - 714
JO - Inflammation Research
JF - Inflammation Research
IS - 7
ER -