gms | German Medical Science

44. Kongress der Deutschen Gesellschaft für Rheumatologie, 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

31.08. - 03.09.2016, Frankfurt am Main

SSc- IgG effects are mediated through distinct pathways in THP-1 cells

Meeting Abstract

  • Georgios Eleftheriadis - Klinik für Rheumatologie, Universität zu Lübeck, Lübeck
  • Melanie Wannick - Klinik für Dermatologie, Universität zu Lübeck, Lübeck
  • Christian David Sadik - Klinik für Dermatologie, Universität zu Lübeck, Lübeck
  • Gabriela Riemekasten - Klinik für Rheumatologie, Universität zu Lübeck, Lübeck

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Frankfurt am Main, 31.08.-03.09.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocER.25

doi: 10.3205/16dgrh177, urn:nbn:de:0183-16dgrh1773

Veröffentlicht: 29. August 2016

© 2016 Eleftheriadis et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Background: Peripheral-blood-mononuclear-cells (PBMCs) are thought to play a key role in the pathogenesis and progress of systemic scleroderma (SSc) with patients displaying distinct shifts in count, receptor expression profile and cytokine secretion patterns. SSc-IgG with elevated anti-AT1R (angiotensin II type 1 receptor )/ETAR (endothelin-1 type A receptor) -AAb (autoantibody) titers has been correlated to disease severity and progression. It remains poorly understood through which pathways SSc- IgG mediates its effects.

In this study we sought to analyze the expression patterns of THP-1 cells (a monocytic cell line) after SSc-IgG application and their reversibility through application of numerous pharmacological inhibitors.

Methods: Transcription of IL-8- and CCL-18 in THP-1-cells after SSc-IgG and normal IgG stimulation was quantified by qPCR. Stimulations of THP-1 cells with total IgG of phenotypically different groups of SSc-patients as well as ET-1 and AT-2 were carried out. In addition, stimulation with pharmacological inhibitors was conducted in a dose-dependent-manner. The results were quantified by IL-8-ELISA of the supernatants.

Results: Transcription of IL-8 and CCL-18 is induced by SSc-IgG treatment in comparison to normal IgG which does not follow this trend. IL-8 secretion of THP-1 cells upon SSc-IgG stimulation is mediated through specific autoantibody effects and transduced through NF-κB, ERK-, and AP-1 pathways.

Conclusion: A stable cell culture system able to reproduce previous PBMC data on IL-8 and CCL-18 induction upon SSc- IgG-treatment could be established and insight was gained regarding key pathways which are involved in the transduction leading to IL-8 secretion. The effect of specific surface receptor expression profiles on transduction remains to be elucidated.