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Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis

OBJECTIVE: The aim of this study was to examine the pro-inflammatory effects of IL-6 in ex vivo temporal artery explant cultures. METHODS: Patients meeting 1990 ACR classification criteria for GCA were prospectively recruited. Temporal artery biopsies were obtained and temporal artery explants cultu...

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Autores principales: O’Neill, Lorraine, McCormick, Jennifer, Gao, Wei, Veale, Douglas J, McCarthy, Geraldine M, Murphy, Conor C, Fearon, Ursula, Molloy, Eamonn S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649906/
https://www.ncbi.nlm.nih.gov/pubmed/31431999
http://dx.doi.org/10.1093/rap/rkz011
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author O’Neill, Lorraine
McCormick, Jennifer
Gao, Wei
Veale, Douglas J
McCarthy, Geraldine M
Murphy, Conor C
Fearon, Ursula
Molloy, Eamonn S
author_facet O’Neill, Lorraine
McCormick, Jennifer
Gao, Wei
Veale, Douglas J
McCarthy, Geraldine M
Murphy, Conor C
Fearon, Ursula
Molloy, Eamonn S
author_sort O’Neill, Lorraine
collection PubMed
description OBJECTIVE: The aim of this study was to examine the pro-inflammatory effects of IL-6 in ex vivo temporal artery explant cultures. METHODS: Patients meeting 1990 ACR classification criteria for GCA were prospectively recruited. Temporal artery biopsies were obtained and temporal artery explants cultured ex vivo with IL-6 (10–40 ng/ml) in the presence or absence of its soluble receptor (sIL-6R; 20 ng/ml) for 24 h. Explant supernatants were harvested after 24 h and assayed for IFN-γ, TNF-α, Serum amyloid A, IL-1β, IL-17, IL-8, angiotensin II and VEGF by ELISA. Myofibroblast outgrowths, cytoskeletal rearrangement and wound repair assays were performed. RESULTS: IL-6 augmented production of VEGF, but not of any of the other pro-inflammatory mediators assayed. No differences were observed in the explants cultured in the presence or absence of the sIL-6R or between those with a positive (n = 11) or negative (n = 17) temporal artery biopsy. IL-6 did not enhance myofibroblast proliferation or migration. Western blot analysis confirmed signalling activation, with increased expression of pSTAT3 in response to IL-6+sIL-6R. CONCLUSION: IL-6 stimulation of temporal artery explants from patients with GCA neither increased expression of key pro-inflammatory mediators nor influenced myofibroblast proliferation or migration.
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spelling pubmed-66499062019-08-20 Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis O’Neill, Lorraine McCormick, Jennifer Gao, Wei Veale, Douglas J McCarthy, Geraldine M Murphy, Conor C Fearon, Ursula Molloy, Eamonn S Rheumatol Adv Pract Original Article OBJECTIVE: The aim of this study was to examine the pro-inflammatory effects of IL-6 in ex vivo temporal artery explant cultures. METHODS: Patients meeting 1990 ACR classification criteria for GCA were prospectively recruited. Temporal artery biopsies were obtained and temporal artery explants cultured ex vivo with IL-6 (10–40 ng/ml) in the presence or absence of its soluble receptor (sIL-6R; 20 ng/ml) for 24 h. Explant supernatants were harvested after 24 h and assayed for IFN-γ, TNF-α, Serum amyloid A, IL-1β, IL-17, IL-8, angiotensin II and VEGF by ELISA. Myofibroblast outgrowths, cytoskeletal rearrangement and wound repair assays were performed. RESULTS: IL-6 augmented production of VEGF, but not of any of the other pro-inflammatory mediators assayed. No differences were observed in the explants cultured in the presence or absence of the sIL-6R or between those with a positive (n = 11) or negative (n = 17) temporal artery biopsy. IL-6 did not enhance myofibroblast proliferation or migration. Western blot analysis confirmed signalling activation, with increased expression of pSTAT3 in response to IL-6+sIL-6R. CONCLUSION: IL-6 stimulation of temporal artery explants from patients with GCA neither increased expression of key pro-inflammatory mediators nor influenced myofibroblast proliferation or migration. Oxford University Press 2019-05-06 /pmc/articles/PMC6649906/ /pubmed/31431999 http://dx.doi.org/10.1093/rap/rkz011 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
O’Neill, Lorraine
McCormick, Jennifer
Gao, Wei
Veale, Douglas J
McCarthy, Geraldine M
Murphy, Conor C
Fearon, Ursula
Molloy, Eamonn S
Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis
title Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis
title_full Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis
title_fullStr Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis
title_full_unstemmed Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis
title_short Interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis
title_sort interleukin-6 does not upregulate pro-inflammatory cytokine expression in an ex vivo model of giant cell arteritis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649906/
https://www.ncbi.nlm.nih.gov/pubmed/31431999
http://dx.doi.org/10.1093/rap/rkz011
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