CC motif chemokine ligand 13 is associated with rheumatoid arthritis pathogenesis

Vol.23 No.5

Original Article

CC motif chemokine ligand 13 is associated with rheumatoid arthritis pathogenesis

Authors

Ayako Yamaguchi^{1, 2} , Kazuhisa Nozawa^{1, 2} , Maki Fujishiro¹ , Mikiko Kawasaki¹ , Fujihiko Suzuki³ , Kenji Takamori¹ , Hideoki Ogawa¹ , Yoshinari Takasaki² , Iwao Sekigawa^{1, 4}

Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan
Department of Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Department of Pathology, Juntendo University Urayasu Hospital, Chiba, Japan
Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan

Received:

29 November 2011

Accepted:

21 August 2012

Published online:

25 September 2012

Full Text

PDF　(member's only)

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 enzymelinked 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-a). 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.

Key words

Rheumatoid arthritis, CCL13/MCP-4, Apoptosis, Angiogenesis, TNF-α