Skip to main content
main-content

01.08.2011 | Research article | Ausgabe 4/2011 Open Access

Arthritis Research & Therapy 4/2011

High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 4/2011
Autoren:
Heidi Wähämaa, Hanna Schierbeck, Hulda S Hreggvidsdottir, Karin Palmblad, Anne-Charlotte Aveberger, Ulf Andersson, Helena Erlandsson Harris
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​ar3450) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

HW was responsible for the study design, experimental work, data collection and the manuscript preparation. HS participated in study design, experimental work and statistical analysis and in manuscript preparation. HH participated in study design, experimental work and in manuscript preparation. KP performed the immunocytochemical stainings and ACA participated in cell culture work and with technical support during many experiments. UA was responsible for study design, supervision and manuscript preparation. HEH was responsible for study design, supervision and she drafted the manuscript. All authors read and approved the final manuscript.

Abstract

Introduction

In addition to its direct proinflammatory activity, extracellular high mobility group box protein 1 (HMGB1) can strongly enhance the cytokine response evoked by other proinflammatory molecules, such as lipopolysaccharide (LPS), CpG-DNA and IL-1β, through the formation of complexes. Extracellular HMGB1 is abundant in arthritic joint tissue where it is suggested to promote inflammation as intra-articular injections of HMGB1 induce synovitis in mice and HMGB1 neutralizing therapy suppresses development of experimental arthritis. The aim of this study was to determine whether HMGB1 in complex with LPS, interleukin (IL)-1α or IL-1β has enhancing effects on the production of proinflammatory mediators by rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF). Furthermore, we examined the toll-like receptor (TLR) 4 and IL-1RI requirement for the cytokine-enhancing effects of the investigated HMGB1-ligand complexes.

Methods

Synovial fibroblasts obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients were stimulated with HMGB1 alone or in complex with LPS, IL-1α or IL-1β. Tumour necrosis factor (TNF) production was determined by enzyme-linked immunospot assay (ELISPOT) assessment. Levels of IL-10, IL-1-β, IL-6 and IL-8 were measured using Cytokine Bead Array and matrix metalloproteinase (MMP) 3 production was determined by ELISA.

Results

Stimulation with HMGB1 in complex with LPS, IL-1α or IL-1β enhanced production of TNF, IL-6 and IL-8. HMGB1 in complex with IL-1β increased MMP production from both RASF and OASF. The cytokine production was inhibited by specific receptor blockade using detoxified LPS or IL-1 receptor antagonist, indicating that the synergistic effects were mediated through the partner ligand-reciprocal receptors TLR4 and IL-1RI, respectively.

Conclusions

HMGB1 in complex with LPS, IL-1α or IL-1β boosted proinflammatory cytokine- and MMP production in synovial fibroblasts from RA and OA patients. A mechanism for the pathogenic role of HMGB1 in arthritis could thus be through enhancement of inflammatory and destructive mechanisms induced by other proinflammatory mediators present in the arthritic joint.
Zusatzmaterial
Authors’ original file for figure 1
13075_2011_3202_MOESM1_ESM.png
Authors’ original file for figure 2
13075_2011_3202_MOESM2_ESM.pdf
Authors’ original file for figure 3
13075_2011_3202_MOESM3_ESM.pdf
Authors’ original file for figure 4
13075_2011_3202_MOESM4_ESM.eps
Authors’ original file for figure 5
13075_2011_3202_MOESM5_ESM.eps
Authors’ original file for figure 6
13075_2011_3202_MOESM6_ESM.eps
Authors’ original file for figure 7
13075_2011_3202_MOESM7_ESM.pdf
Authors’ original file for figure 8
13075_2011_3202_MOESM8_ESM.pdf
Authors’ original file for figure 9
13075_2011_3202_MOESM9_ESM.pdf
Authors’ original file for figure 10
13075_2011_3202_MOESM10_ESM.pdf
Authors’ original file for figure 11
13075_2011_3202_MOESM11_ESM.pdf
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 4/2011

Arthritis Research & Therapy 4/2011 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

22.05.2019 | DAC 2019 | Kongressbericht | Nachrichten

So macht die Mischinfusion, was sie soll

22.05.2019 | DAC 2019 | Kongressbericht | Nachrichten

Neue Leitlinie "Prolongiertes Weaning" – ein Ausblick

22.05.2019 | DAC 2019 | Kongressbericht | Nachrichten

Juristische Fallstricke am Lebensende

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise