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The p38-mediated rapid down-regulation of cell surface gp130 expression impairs interleukin-6 signaling in the synovial fluid of juvenile idiopathic arthritis patients

 
: Honke, N.; Ohl, K.; Wiener, A.; Bierwagen, J.; Peitz, J.; Fiore, S. di; Fischer, R.; Wagner, N.; Wüller, S.; Tenbrock, K.

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Arthritis & rheumatology 66 (2014), No.2, pp.470-478
ISSN: 2326-5191
ISSN: 2326-5205
English
Journal Article
Fraunhofer IME ()

Abstract
Objective. Interleukin-6 (IL-6) signaling plays an important proinflammatory role, but this role is restricted by regulatory mechanisms that, for example, reduce the cell surface availability of the signaltransducing chain of the IL-6 receptor, gp130. The aim of this study was to determine whether the inflammatory environment in arthritic joints has an impact on monocytic gp130 surface expression and the extent to which regulatory processes in the synovial fluid (SF) can be reproduced in an in vitro model.
Methods. Flow cytometry and live cell imaging were used to measure the cell surface expression and internalization of gp130. STAT-3 phosphorylation was monitored by flow cytometry and Western blotting.
Results. In patients with juvenile idiopathic arthritis (JIA), levels of cell surface gp130 expression in SF monocytes were reduced compared to those in peripheral blood (PB) monocytes. These reduced levels were reproduced when PB monocytes from healthy donors were stim ulated with SF, and this reduction was dependent on p38 MAPK. The induction of p38 by IL-1 in PB monocytes interfered with IL-6 signaling due to the reduced cell surface expression of gp130.
Conclusion. These results suggest that p38- mediated proinflammatory stimuli induce the downregulation of gp130 on monocytes and thus restrict gp130-mediated signal transduction. This regulatory mechanism could be of relevance to processes in the inflamed joints of patients with JIA.

: http://publica.fraunhofer.de/documents/N-301675.html