PGLYRP-2 and Nod2 Are Both Required for Peptidoglycan-Induced Arthritis and Local Inflammation

Sukumar Saha, Jin Qi, Shiyong Wang, Minhui Wang, Xinna Li, Yungi Kim, Gabriel Núñez, Dipika Gupta, Roman Dziarski

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)137-150
Number of pages14
JournalCell Host and Microbe
Volume5
Issue number2
DOIs
Publication statusPublished - 2009 Feb 19
Externally publishedYes

Fingerprint

Peptidoglycan
Arthritis
Inflammation
Toll-Like Receptor 4
amidase
Insects
Neutrophil Infiltration
Chemokines
Mammals
Neutrophils
Anti-Inflammatory Agents
Extremities
peptidoglycan recognition protein

Keywords

  • CELLBIO
  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

PGLYRP-2 and Nod2 Are Both Required for Peptidoglycan-Induced Arthritis and Local Inflammation. / Saha, Sukumar; Qi, Jin; Wang, Shiyong; Wang, Minhui; Li, Xinna; Kim, Yungi; Núñez, Gabriel; Gupta, Dipika; Dziarski, Roman.

In: Cell Host and Microbe, Vol. 5, No. 2, 19.02.2009, p. 137-150.

Research output: Contribution to journalArticle

Saha, S, Qi, J, Wang, S, Wang, M, Li, X, Kim, Y, Núñez, G, Gupta, D & Dziarski, R 2009, 'PGLYRP-2 and Nod2 Are Both Required for Peptidoglycan-Induced Arthritis and Local Inflammation', Cell Host and Microbe, vol. 5, no. 2, pp. 137-150. https://doi.org/10.1016/j.chom.2008.12.010
Saha, Sukumar ; Qi, Jin ; Wang, Shiyong ; Wang, Minhui ; Li, Xinna ; Kim, Yungi ; Núñez, Gabriel ; Gupta, Dipika ; Dziarski, Roman. / PGLYRP-2 and Nod2 Are Both Required for Peptidoglycan-Induced Arthritis and Local Inflammation. In: Cell Host and Microbe. 2009 ; Vol. 5, No. 2. pp. 137-150.
@article{c07f4b743e6b4d4b8a4171c2b5e51c58,
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.",
keywords = "CELLBIO, MICROBIO, MOLIMMUNO",
author = "Sukumar Saha and Jin Qi and Shiyong Wang and Minhui Wang and Xinna Li and Yungi Kim and Gabriel N{\'u}{\~n}ez and Dipika Gupta and Roman Dziarski",
year = "2009",
month = "2",
day = "19",
doi = "10.1016/j.chom.2008.12.010",
language = "English",
volume = "5",
pages = "137--150",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "2",

}

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, Yungi

AU - Núñez, Gabriel

AU - Gupta, Dipika

AU - Dziarski, Roman

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

VL - 5

SP - 137

EP - 150

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 2

ER -