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PReS-FINAL-2085: The p38-mediated rapid downregulation of cell surface gp130 expression impairs IL-6 signaling in the synovial fluid of juvenile idiopathic arthritis patients
© Honke et al.; licensee BioMed Central Ltd. 2013
Published: 5 December 2013
In patients with juvenile idiopathic arthritis (JIA) high levels of IL-6 are present in the serum and synovial fluid (SF). IL-6 signaling plays an important pro-inflammatory role but is restricted by regulatory mechanisms such as reducing the cell surface availability of the signal-transducing chain of the IL-6 receptor (gp130).
The aim of this study was to determine whether the inflammatory environment in the arthritic joint has an impact on monocytic gp130 surface expression and the extent to which regulatory processes in the SF can be transferred to an in vitro model.
Flow cytometry and live-cell imaging were used to measure the cell surface expression and internalization of gp130. STAT3 phosphorylation was monitored by flow cytometry and western blotting.
The level of cell surface gp130 expression on SF monocytes was reduced compared to peripheral blood (PB) monocytes from patients with JIA. This reduction could be reproduced by stimulating PB monocytes from healthy donors with SF and was dependent on p38 MAPK. The induction of p38 by IL-1β in PB monocytes interfered with IL-6 signaling due to the reduced cell surface expression of gp130.
The results suggest that p38-mediated pro-inflammatory stimuli induce the downregulation of gp130 on monocytes and thus restrict gp130-mediated signal transduction. This regulatory mechanism could be relevant in the inflamed joints of patients with JIA.
Disclosure of interest
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.