Universität zu Köln

Honke, Nora, Ohl, Kim, Wiener, Anastasia, Bierwagen, Jeff, Peitz, Joachim, Di Fiore, Stefano, Fischer, Rainer, Wagner, Norbert, Wueller, Stefan and Tenbrock, Klaus (2014). The p38-Mediated Rapid Down-Regulation of Cell Surface gp130 Expression Impairs Interleukin-6 Signaling in the Synovial Fluid of Juvenile Idiopathic Arthritis Patients. Arthritis Rheumatol., 66 (2). S. 470 - 479. HOBOKEN: WILEY. ISSN 2326-5205

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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 signal-transducing 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 stimulated with SF, and this reduction was dependent on p38 MAPK. The induction of p38 by IL-1 beta 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 down-regulation 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Honke, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Ohl, Kim UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiener, Anastasia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bierwagen, Jeff UNSPECIFIED UNSPECIFIED UNSPECIFIED Peitz, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Di Fiore, Stefano UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Wueller, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Tenbrock, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-446108
DOI:	10.1002/art.38245
Journal or Publication Title:	Arthritis Rheumatol.
Volume:	66
Number:	2
Page Range:	S. 470 - 479
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2326-5205
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOCS3 MESSENGER-RNA; RHEUMATOID-ARTHRITIS; TNF-ALPHA; T-CELLS; IL-6; CYTOKINE; ACTIVATION; MONOCYTES; INTERNALIZATION; IDENTIFICATION Multiple languages Rheumatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44610