Osteoarthritis-associated basic calcium phosphate crystals induce pro-inflammatory cytokines and damage-associated molecules via activation of Syk and PI3 kinase

Osteoarthritis-associated basic calcium phosphate crystals induce pro-inflammatory cytokines and damage-associated molecules via activation of Syk and PI3 kinase

Copyright © 2012 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 144(2012), 3 vom: 15. Sept., Seite 228-36
1. Verfasser: Cunningham, Clare C (VerfasserIn)
Weitere Verfasser: Mills, Evanna, Mielke, Lisa A, O'Farrell, Laura K, Lavelle, Ed, Mori, Andrés, McCarthy, Geraldine M, Mills, Kingston H G, Dunne, Aisling
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2012
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Calcium Phosphates Calgranulin A Interleukin-18 Interleukin-1alpha Interleukin-1beta Intracellular Signaling Peptides and Proteins S100a8 protein, mouse Phosphatidylinositol 3-Kinases mehr... EC 2.7.1.- Protein-Tyrosine Kinases EC 2.7.10.1 SYK protein, human EC 2.7.10.2 Syk Kinase Syk protein, mouse Extracellular Signal-Regulated MAP Kinases EC 2.7.11.24
Beschreibung
Zusammenfassung:Copyright © 2012 Elsevier Inc. All rights reserved.
The pro-inflammatory cytokines, TNFα, IL-1 and IL-18, amplify cartilage destruction associated with osteoarthritis (OA). Current data suggest that basic calcium phosphate (BCP) crystals are potent drivers of inflammatory mediator and matrix metalloprotease expression in the OA joint. It has previously been demonstrated that synovial macrophages play a role in initiating and driving BCP-induced inflammation. However, the molecular mechanisms by which BCP crystals exert their effects remain unclear. Here we demonstrate that exposure of macrophages to BCP crystals leads to activation of Syk and PI3 kinase. Furthermore, we show that production of pro-inflammatory cytokines and phosphorylation of the downstream kinase, ERK, are suppressed following treatment with Syk and PI3 kinase inhibitors. Finally, we demonstrate that treatment of macrophages with BCP crystals induces the production of the damage-associated molecule, S100A8, in a Syk dependent manner. We therefore identify Syk and PI3 kinase as potential novel targets for the treatment of BCP-related pathologies
Beschreibung:Date Completed 07.11.2012
Date Revised 25.11.2016
published: Print-Electronic
CommentIn: Clin Immunol. 2012 Sep;144(3):283-4. doi: 10.1016/j.clim.2012.07.009. - PMID 22885814
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2012.06.007