Protein synthesis of the pro-inflammatory S100A8-A9 complex in plasmacytoid dendritic cells and cell surface S100A8-A9 on leukocyte subpopulations in systemic lupus erythematosusReport as inadecuate




Protein synthesis of the pro-inflammatory S100A8-A9 complex in plasmacytoid dendritic cells and cell surface S100A8-A9 on leukocyte subpopulations in systemic lupus erythematosus - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 13:R60

First Online: 14 April 2011Received: 17 December 2010Revised: 10 March 2011Accepted: 14 April 2011

Abstract

IntroductionSystemic lupus erythematosus SLE is an autoimmune disease with chronic or episodic inflammation in many different organ systems, activation of leukocytes and production of pro-inflammatory cytokines. The heterodimer of the cytosolic calcium-binding proteins S100A8 and S100A9 S100A8-A9 is secreted by activated polymorphonuclear neutrophils PMNs and monocytes and serves as a serum marker for several inflammatory diseases. Furthermore, S100A8 and S100A9 have many pro-inflammatory properties such as binding to Toll-like receptor 4 TLR4. In this study we investigated if aberrant cell surface S100A8-A9 could be seen in SLE and if plasmacytoid dendritic cells pDCs could synthesize S100A8-A9.

MethodsFlow cytometry, confocal microscopy and real-time PCR of flow cytometry-sorted cells were used to measure cell surface S100A8-A9, intracellular S100A8-A9 and mRNA levels of S100A8 and S100A9, respectively.

ResultsCell surface S100A8-A9 was detected on all leukocyte subpopulations investigated except for T cells. By confocal microscopy, real-time PCR and stimulation assays, we could demonstrate that pDCs, monocytes and PMNs could synthesize S100A8-A9. Furthermore, pDC cell surface S100A8-A9 was higher in patients with active disease as compared to patients with inactive disease. Upon immune complex stimulation, pDCs up-regulated the cell surface S100A8-A9. SLE patients had also increased serum levels of S100A8-A9.

ConclusionsPatients with SLE had increased cell surface S100A8-A9, which could be important in amplification and persistence of inflammation. Importantly, pDCs were able to synthesize S100A8-A9 proteins and up-regulate the cell surface expression upon immune complex-stimulation. Thus, S100A8-A9 may be a potent target for treatment of inflammatory diseases such as SLE.

AbbreviationsGAGglycosaminoglycans

ICimmune complex

IFNinterferon

mDCmyeloid dendritic cell

MFImean fluorescence index

NETneutrophils extracellular trap

PBMCperipheral blood mononuclear cell

pDCplasmacytoid dendritic cell

PMNpolymorphonuclear neutrophil

RAGEreceptor for advanced glycation end products

RNPribonuclear protein

SLEsystemic lupus erythematosus

TLRtoll like receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3314 contains supplementary material, which is available to authorized users.

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Author: Christian Lood - Martin Stenström - Helena Tydén - Birgitta Gullstrand - Eva Källberg - Tomas Leanderson - Lennart Trued

Source: https://link.springer.com/







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