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CC motif chemokine ligand 13 is associated with rheumatoid arthritis pathogenesis

  • Original Article
  • Published:
Modern Rheumatology

Abstract

Objectives

CC motif chemokines are considered to be implicated in the pathogenesis of rheumatoid arthritis (RA) via recruitment of monocytes and lymphocytes. CC motif chemokine ligand 13 (CCL13)/monocyte chemoattractant protein-4 (MCP-4) is postulated to be a potent RA inducer. We conducted a study to more precisely clarify the role of CCL13 in RA pathogenesis.

Methods

CCL13 expression was evaluated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining in serum samples and synovial tissues from RA patients. The effects of CCL13 against apoptosis were monitored on cultured synovial fibroblasts. The chemoattractant activity of CCL13 was evaluated by the Boyden chamber assay in monocytes (THP-1 cells) and human umbilical vein endothelial cells (HUVECs).

Results

We found that CCL13 serum level and synovial tissue expression were increased in RA patients. CCL13 had chemoattractant activity for both THP-1 cells and HUVECs. Interestingly, CCL13 expression was positively regulated by tumor necrosis factor-alpha (TNF-α). Furthermore, apoptosis induced by hydrogen peroxide (H2O2) and serum deprivation was inhibited by CCL13 on the cultured synovial fibroblasts.

Conclusions

CCL13 may be associated with disease progression as a result of its antiapoptotic effects, increased macrophage infiltration, and synovial tissue angiogenesis in RA patients.

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Acknowledgments

This work was supported by a grant from the Institute for Environment and Gender-specific Medicine, Juntendo University Graduate School of Medicine and, a Health and Labor Science Research Grant (Grant Name: Research on the obstetrical management of women with autoantibodies).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan

    Ayako Yamaguchi, Kazuhisa Nozawa, Maki Fujishiro, Mikiko Kawasaki, Kenji Takamori, Hideoki Ogawa & Iwao Sekigawa

  2. Department of Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Ayako Yamaguchi, Kazuhisa Nozawa & Yoshinari Takasaki

  3. Department of Pathology, Juntendo University Urayasu Hospital, Chiba, Japan

    Fujihiko Suzuki

  4. Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan

    Iwao Sekigawa

Authors
  1. Ayako Yamaguchi
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  2. Kazuhisa Nozawa
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  3. Maki Fujishiro
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  4. Mikiko Kawasaki
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  5. Fujihiko Suzuki
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  6. Kenji Takamori
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  7. Hideoki Ogawa
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  8. Yoshinari Takasaki
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  9. Iwao Sekigawa
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Corresponding author

Correspondence to Kazuhisa Nozawa.

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Yamaguchi, A., Nozawa, K., Fujishiro, M. et al. CC motif chemokine ligand 13 is associated with rheumatoid arthritis pathogenesis. Mod Rheumatol 23, 856–863 (2013). https://doi.org/10.1007/s10165-012-0752-4

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  • DOI: https://doi.org/10.1007/s10165-012-0752-4

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