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Cells. 2019 Jun 9;8(6). pii: E561. doi: 10.3390/cells8060561.

Peficitinib Inhibits the Chemotactic Activity of Monocytes via Proinflammatory Cytokine Production in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

Author information

1
Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo 142-8555, Japan. y.ikari@live.jp.
2
Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo 142-8555, Japan. t.isozaki@med.showa-u.ac.jp.
3
Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo 142-8555, Japan. tsubokura@cnt.showa-u.ac.jp.
4
Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo 142-8555, Japan. tkasama@med.showa-u.ac.jp.

Abstract

Background: This study was performed to examine the effects of the Janus kinase (JAK) inhibitor peficitinib on fibroblast-like synoviocytes (FLS) obtained from patients with rheumatoid arthritis (RA). Methods: To examine the expression of JAK1, JAK2, and JAK3 in RA synovial tissue (ST) and FLS, immunohistochemistry was performed. We investigated the effects of peficitinib on interleukin 6 and IL-6 receptor responses in RA FLS. Phosphorylation of STAT was determined by western blot. To examine the functional analysis of peficitinib, we performed a proliferation and chemotaxis assays with FLS using THP-1 and peripheral blood mononuclear cells (PBMC). The inflammatory mediator expression of FLS was estimated by enzyme-linked immunosorbent assay. Results: JAK1, JAK2, and JAK3 were expressed in RA STs and FLS. Phosphorylation of STAT1, STAT3, and STAT5 in RA FLS was suppressed by peficitinib in a concentration-dependent manner. Peficitinib-treated RA FLS-conditioned medium reduced THP-1 and PBMC migration (p < 0.05) and proliferation of RA FLS (p < 0.05). Peficitinib suppressed the secretion of MCP-1/CCL2 in the RA FLS supernatant (p < 0.05). Conclusion: Peficitinib suppressed the JAK-STAT pathway in RA FLS and also suppressed monocyte chemotaxis and proliferation of FLS through inhibition of inflammatory cytokines.

KEYWORDS:

fibroblast-like synoviocytes; monocyte chemotaxis; peficitinib; rheumatoid arthritis

PMID:
31181818
DOI:
10.3390/cells8060561
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