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: Holly L Rosenzweig, Jenna S Clowers, Gabriel Nunez, James T Rosenbaum, Michael P Davey
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 60 Issue 7 Pg. 705-14 (Jul 2011) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 21424514 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Lectins, C-Type
• Membrane Proteins
• Nerve Tissue Proteins
• Nod2 Signaling Adaptor Protein
• Nod2 protein, mouse
• Toll-Like Receptors
• beta-Glucans
• dectin 1
• dectin-2, mouse
• curdlan
• Zymosan
• Cathepsins

Topics

• Animals
• Arthritis, Experimental (chemically induced, immunology, pathology)
• Cathepsins (metabolism)
• Disease Models, Animal
• Immunity, Innate
• Joints (pathology)
• Lectins, C-Type (metabolism)
• Membrane Proteins (metabolism)
• Mice
• Mice, Knockout
• Nerve Tissue Proteins (metabolism)
• Nod2 Signaling Adaptor Protein (genetics, metabolism)
• Signal Transduction (physiology)
• Toll-Like Receptors (metabolism)
• Zymosan (immunology)
• beta-Glucans (immunology)