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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages

Authors: Takuya Matsumoto, Nobunori Takahashi, Toshihisa Kojima, Yutaka Yoshioka, Jun Ishikawa, Koichi Furukawa, Kenji Ono, Makoto Sawada, Naoki Ishiguro, Akihito Yamamoto

Published in: Arthritis Research & Therapy | Issue 1/2016

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Abstract

Background

The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis.

Methods

DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using a physiologic arthritis score, histological analysis, serum tumor necrosis factor (TNF)-α concentration, and the proportion of forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. In vivo biofluorescence imaging was used to assess the distribution of sSiglec-9. Levels of M1 (TNF-α, interleukin [IL]-6, and inducible nitric oxide synthase) and M2 (CD206, Arginase-1, and IL-10) macrophage markers and phosphorylation of intracellular signaling molecules were examined in macrophages, and levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were examined in FLS.

Results

sSiglec-9 significantly suppressed the clinical and histological incidence and severity of arthritis. The proportion of Foxp3-positive Treg cells significantly improved and serum TNF-α concentration decreased in vivo. Although sSiglec-9 reduced the expression of M1 markers in macrophages, it did not affect the expression of M2 markers and MMPs in FLS. Nuclear factor (NF)-kB p65 phosphorylation was attenuated by sSiglec-9, and chemical blockade of the NF-kB pathway reduced M1 marker expression in RAW264.7 cells.

Conclusions

In this study, we have demonstrated the therapeutic effects of sSiglec-9 in a murine CIA model. The mechanism underlying these effects involves the suppression of M1 proinflammatory macrophages by inhibiting the NF-kB pathway. sSiglec-9 may provide a novel therapeutic option for patients with rheumatoid arthritis refractory to currently available drugs.
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Metadata
Title
Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages
Authors
Takuya Matsumoto
Nobunori Takahashi
Toshihisa Kojima
Yutaka Yoshioka
Jun Ishikawa
Koichi Furukawa
Kenji Ono
Makoto Sawada
Naoki Ishiguro
Akihito Yamamoto
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1035-9

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Keynote webinar | Spotlight on medication adherence

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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