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Inhibition of JNK in synovium by treatment with golimumab in rheumatoid arthritis

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Abstract

The aim of this study was to investigate immunohistological changes in mitogen-activated protein kinases (MAPKs) in the synovium following treatment with golimumab, compared with methotrexate (MTX). We assessed synovial tissues for 13 different molecules to detect cytokine levels histologically from 10 methotrexate (MTX)-treated rheumatoid arthritis (RA) patients as controls and 10 golimumab plus MTX-treated RA patients. Synovium samples from both groups were assessed by hematoxylin and eosin (HE) staining and analyzed for expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD4 (T cells), CD8 (T cells), CD20 (B cells), CD68 (macrophages), receptor activator of nuclear (kappa) B ligand (RANKL), bromodeoxyuridine (BrdU), CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (ERK1/ERK2), and phospho-c-Jun N-terminal kinase (JNK), by an immunohistological examination. HE staining showed that there was a significant decrease in cell proliferation in the synovium in RA patients who received golimumab compared with the controls. TNF-α, IL-6, MMP3, BrdU, p38, and ERK were not seen at significant levels in either group. On the other hand, CD4, CD8, CD20, CD29, CD68, RANKL, and JNK were significantly decreased in the golimumab group compared with the control. Based on a histological analysis of the synovium, it appears that the efficacy of the treatment with golimumab may involve the inhibition of cell proliferation, with decreases in T cells, B cells, macrophages, β-1 integrin, RANKL, and JNK in the synovium, compared with MTX treatment, in RA.

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Acknowledgments

This work was supported in part by a grant-in-aid for Scientific Research (KAKENHI) (C) (24592284) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan Society for the Promotion of Science (JSPS).

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  1. Department of Orthopaedic Surgery, Tokyo Women’s Medical University, Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo, 116-8567, Japan

    Katsuaki Kanbe, Junji Chiba & Atsushi Nakamura

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  1. Katsuaki Kanbe
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  2. Junji Chiba
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  3. Atsushi Nakamura
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Correspondence to Katsuaki Kanbe.

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Kanbe, K., Chiba, J. & Nakamura, A. Inhibition of JNK in synovium by treatment with golimumab in rheumatoid arthritis. Rheumatol Int 34, 125–130 (2014). https://doi.org/10.1007/s00296-012-2626-7

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