TY - JOUR
T1 - PGLYRP-2 and Nod2 Are Both Required for Peptidoglycan-Induced Arthritis and Local Inflammation
AU - Saha, Sukumar
AU - Qi, Jin
AU - Wang, Shiyong
AU - Wang, Minhui
AU - Li, Xinna
AU - Kim, Yun Gi
AU - Núñez, Gabriel
AU - Gupta, Dipika
AU - Dziarski, Roman
N1 - Funding Information:
We are grateful to Grégoire Lauvau for providing TLR-2 −/− , TLR-4 −/− , and MyD88 −/− mice; to Robert Rukavina for maintaining and breeding our mice; and to Patrick Bankston for help in interpreting histology slides. This work was supported by USPHS Grants AI28797 and AI56395 from NIH to R.D. and D.G. and DK61707 to G.N. The authors have no conflict of interest.
PY - 2009/2/19
Y1 - 2009/2/19
N2 - Peptidoglycan recognition proteins (PGRPs) are structurally conserved from insects to mammals. Insect PGRPs have diverse host-defense functions. Mammalian PGRPs PGLYRP-1, PGLYRP-3, and PGLYRP-4 have bactericidal activity, while PGLYRP-2 has amidase activity. To extend the known functions of mammalian PGRPs, we examined whether they have immunomodulating activities in peptidoglycan-induced arthritis in mice. We demonstrate that PGLYRP-2 and Nod2 are both required for arthritis in this model. The sequence of events in peptidoglycan-induced arthritis is activation of Nod2, local expression of PGLYRP-2, chemokine production, and recruitment of neutrophils into the limbs, which induces acute arthritis. Only PGLYRP-2 among the four mammalian PGRPs displays this proinflammatory function, and PGLYRP-1 is anti-inflammatory. Toll-like receptor 4 (TLR4) and MyD88 are required for maturation of neutrophils before peptidoglycan challenge. Our results demonstrate that PGRPs, Nod2, and TLR4, representing three different types of pattern-recognition molecules, play interdependent in vivo roles in local inflammation.
AB - Peptidoglycan recognition proteins (PGRPs) are structurally conserved from insects to mammals. Insect PGRPs have diverse host-defense functions. Mammalian PGRPs PGLYRP-1, PGLYRP-3, and PGLYRP-4 have bactericidal activity, while PGLYRP-2 has amidase activity. To extend the known functions of mammalian PGRPs, we examined whether they have immunomodulating activities in peptidoglycan-induced arthritis in mice. We demonstrate that PGLYRP-2 and Nod2 are both required for arthritis in this model. The sequence of events in peptidoglycan-induced arthritis is activation of Nod2, local expression of PGLYRP-2, chemokine production, and recruitment of neutrophils into the limbs, which induces acute arthritis. Only PGLYRP-2 among the four mammalian PGRPs displays this proinflammatory function, and PGLYRP-1 is anti-inflammatory. Toll-like receptor 4 (TLR4) and MyD88 are required for maturation of neutrophils before peptidoglycan challenge. Our results demonstrate that PGRPs, Nod2, and TLR4, representing three different types of pattern-recognition molecules, play interdependent in vivo roles in local inflammation.
KW - CELLBIO
KW - MICROBIO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=60649087337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60649087337&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2008.12.010
DO - 10.1016/j.chom.2008.12.010
M3 - Article
C2 - 19218085
AN - SCOPUS:60649087337
SN - 1931-3128
VL - 5
SP - 137
EP - 150
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -