title: PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation.
abstract: 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.
authors.affiliation: Indiana University School of Medicine Northwest, Gary, IN 46408, USA.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Saha
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.forename: Shiyong
authors.initials: S
authors.lastname: Wang
authors.forename: Minhui
authors.initials: M
authors.lastname: Wang
authors.forename: Xinna
authors.initials: X
authors.lastname: Li
authors.forename: Yun-Gi
authors.initials: YG
authors.lastname: Kim
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Dipika
authors.initials: D
authors.lastname: Gupta
authors.forename: Roman
authors.initials: R
authors.lastname: Dziarski
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology; D001424:Bacterial Infections / Q000276:immunology* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009238:N-Acetylmuramoyl-L-alanine Amidase; D009504:Neutrophils / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology*; D011506:Proteins / Q000276:immunology*
chemical_list: D018925:Chemokines; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D010457:Peptidoglycan; D011506:Proteins; D009238:N-Acetylmuramoyl-L-alanine Amidase; C416533:Pglyrp2 protein, mouse