Nerve growth factor downregulates inflammatory response in human monocytes through TrkA (Articolo in rivista)

Type
Label
  • Nerve growth factor downregulates inflammatory response in human monocytes through TrkA (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.4049/jimmunol.1300825 (literal)
Alternative label
  • Prencipe G. 1; Minnone G. 1,2 ; Strippoli R.1,3; De Pasquale L. 1; Petrini S. 4; Caiello I. 1; Manni L. 5; De Benedetti F. 1; Bracci-Laudiero L. 1,5 (2014)
    Nerve growth factor downregulates inflammatory response in human monocytes through TrkA
    in The journal of immunology (1950. Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Prencipe G. 1; Minnone G. 1,2 ; Strippoli R.1,3; De Pasquale L. 1; Petrini S. 4; Caiello I. 1; Manni L. 5; De Benedetti F. 1; Bracci-Laudiero L. 1,5 (literal)
Pagina inizio
  • 3345 (literal)
Pagina fine
  • 3354 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.scopus.com/inward/record.url?eid=2-s2.0-84897555497&partnerID=q2rCbXpz (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 192 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 7 (literal)
Note
  • Scopu (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Research Laboratories, Unit of Rheumatology, Bambino Gesù Children's Hospital, 00165 Rome, Italy; 2 Department of Medicine, \"Tor Vergata\" University, Rome 00173, Italy; 3 Department of Cellular Biotechnologies and Haematology, University of Rome La Sapienza, Rome 00185, Italy; 4 Research Laboratories, Confocal Microscopy Core Facility, Bambino Gesù Children's Hospital, 00165 Rome, Italy 5 Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy (literal)
Titolo
  • Nerve growth factor downregulates inflammatory response in human monocytes through TrkA (literal)
Abstract
  • Nerve growth factor (NGF) levels are highly increased in inflamed tissues, but their role is unclear. We show that NGF is part of a regulatory loop in monocytes: inflammatory stimuli, while activating a proinflammatory response through TLRs, upregulate the expression of the NGF receptor TrkA. In turn, NGF, by binding to TrkA, interferes with TLR responses. In TLR-activated monocytes, NGF reduces inflammatory cytokine production (IL-1?, TNF-?, IL-6, and IL-8) while inducing the release of antiinflammatory mediators (IL-10 and IL-1 receptor antagonist). NGF binding to TrkA affects TLR signaling, favoring pathways that mediate inhibition of inflammatory responses: it increases Akt phosphorylation, inhibits glycogen synthase kinase 3 activity, reduces IkB phosphorylation and p65 NF-?B translocation, and increases nuclear p50 NF-?B binding activity. Use of TrkA inhibitors in TLR-activated monocytes abolishes the effects of NGF on the activation of anti-inflammatory signaling pathways, thus increasing NF-?B pathway activation and inflammatory cytokine production while reducing IL-10 production. PBMC and mononuclear cells obtained from the synovial fluid of patients with juvenile idiopathic arthritis show marked downregulation of TrkA expression. In ex vivo experiments, the addition of NGF to LPS-activated juvenile idiopathic arthritis to both mononuclear cells from synovial fluid and PBMC fails to reduce the production of IL-6 that, in contrast, is observed in healthy donors. This suggests that defective TrkA expression may facilitate proinflammatory mechanisms, contributing to chronic tissue inflammation and damage. In conclusion, this study identifies a novel regulatory mechanism of inflammatory responses through NGF and its receptor TrkA, for which abnormality may have pathogenic implications for chronic inflammatory diseases. The Journal of Immunology, 2014, 192: 3345-3354. © Copyright 2014 by The American Association of Immunologists, Inc. All rights reserved. (literal)
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