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Dectin-1 and NOD2 mediate cathepsin activation in zymosan-induced arthritis in mice

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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.

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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.

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Authors and Affiliations

  1. Oregon Health and Science University, Mail stop: L467 AD, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA

    Holly L. Rosenzweig, Jenna S. Clowers, James T. Rosenbaum & Michael P. Davey

  2. VA Medical Center, Portland, OR, USA

    Holly L. Rosenzweig, Jenna S. Clowers & Michael P. Davey

  3. University of Michigan Medical School, Ann Arbor, MI, USA

    Gabriel Nunez

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  1. Holly L. Rosenzweig
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  2. Jenna S. Clowers
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Correspondence to Holly L. Rosenzweig.

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Rosenzweig, H.L., Clowers, J.S., Nunez, G. et al. Dectin-1 and NOD2 mediate cathepsin activation in zymosan-induced arthritis in mice. Inflamm. Res. 60, 705–714 (2011). https://doi.org/10.1007/s00011-011-0324-7

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  • DOI: https://doi.org/10.1007/s00011-011-0324-7

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