Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures.

Hdl Handle:
http://hdl.handle.net/10147/217636
Title:
Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures.
Authors:
Ultaigh, Sinéad Nic An; Saber, Tajvur P; McCormick, Jennifer; Connolly, Mary; Dellacasagrande, Jerome; Keogh, Brian; McCormack, William; Reilly, Mary; O'Neill, Luke A; McGuirk, Peter; Fearon, Ursula; Veale, Douglas J
Affiliation:
Department of Rheumatology, St Vincent's University Hospital, Dublin Academic Medical Centre, Elm Park, Dublin 4, Ireland. douglas.veale@ucd.ie
Citation:
Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures. 2011, 13 (1):R33 Arthritis Res. Ther.
Journal:
Arthritis research & therapy
Issue Date:
2011
URI:
http://hdl.handle.net/10147/217636
DOI:
10.1186/ar3261
PubMed ID:
21345222
Abstract:
The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells.; RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg/ml), an anti-TLR2 antibody (OPN301, 1 μg/ml) or an immunoglobulin G (IgG) (1 μg/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology.; Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab.; These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.
Language:
en
MeSH:
Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Cell Culture Techniques; Cytokines; Female; Humans; Immunohistochemistry; Male; Middle Aged; Synovial Membrane; Toll-Like Receptor 2
ISSN:
1478-6362
Ethical Approval:
N/A

Full metadata record

DC FieldValue Language
dc.contributor.authorUltaigh, Sinéad Nic An-
dc.contributor.authorSaber, Tajvur P-
dc.contributor.authorMcCormick, Jennifer-
dc.contributor.authorConnolly, Mary-
dc.contributor.authorDellacasagrande, Jerome-
dc.contributor.authorKeogh, Brian-
dc.contributor.authorMcCormack, William-
dc.contributor.authorReilly, Mary-
dc.contributor.authorO'Neill, Luke A-
dc.contributor.authorMcGuirk, Peter-
dc.contributor.authorFearon, Ursula-
dc.contributor.authorVeale, Douglas J-
dc.date.accessioned2012-04-04T11:18:52Z-
dc.date.available2012-04-04T11:18:52Z-
dc.date.issued2011-
dc.identifier.citationBlockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures. 2011, 13 (1):R33 Arthritis Res. Ther.-
dc.identifier.issn1478-6362-
dc.identifier.pmid21345222-
dc.identifier.doi10.1186/ar3261-
dc.identifier.urihttp://hdl.handle.net/10147/217636-
dc.description.abstractThe aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells.-
dc.description.abstractRA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg/ml), an anti-TLR2 antibody (OPN301, 1 μg/ml) or an immunoglobulin G (IgG) (1 μg/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology.-
dc.description.abstractPam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab.-
dc.description.abstractThese findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.-
dc.language.isoen-
dc.rightsArchived with thanks to Arthritis research & therapyen_GB
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntirheumatic Agents-
dc.subject.meshArthritis, Rheumatoid-
dc.subject.meshCell Culture Techniques-
dc.subject.meshCytokines-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshSynovial Membrane-
dc.subject.meshToll-Like Receptor 2-
dc.titleBlockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures.en_GB
dc.contributor.departmentDepartment of Rheumatology, St Vincent's University Hospital, Dublin Academic Medical Centre, Elm Park, Dublin 4, Ireland. douglas.veale@ucd.ie-
dc.identifier.journalArthritis research & therapy-
dc.type.qualificationlevelN/Aen
cr.approval.ethicalN/Aen
dc.description.provinceLeinsteren
dc.description.provinceLeinster-

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.