Comparison of anti-inflammatory and anti-angiogenic effects of JAK inhibitors in IL-6 and TNFα-stimulated fibroblast-like synoviocytes derived from patients with RA
Yoshihito Suda, Kemmei Ikuta, Shinya Hayashi, Kensuke Wada, Kensuke Anjiki, Tomoyuki Kamenaga, Masanori Tsubosaka, Yuichi Kuroda, Naoki Nakano, Toshihisa Maeda, Ken Tsumiyama, Tomoyuki Matsumoto, Ryosuke Kuroda, Tsukasa Matsubara
Abstract
Rheumatoid arthritis (RA) involves synovial tissue proliferation, inflammation, and angiogenesis, and contributes to joint destruction. Angiogenesis is a key therapeutic target for the treatment of RA, and Janus kinase (JAK) inhibitors have emerged as a promising therapy. In this study, we compared the inhibitory effects of five JAK inhibitors, including tofacitinib (TOF), baricitinib, peficitinib, upadacitinib, and filgotinib, on interleukin (IL)-6-induced inflammation in RA synovial tissues. All five inhibitors effectively suppressed IL-6-induced inflammatory and angiogenic factors, including vascular endothelial growth factor, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3. Overall, the results suggest that while all five JAK inhibitors are effective in reducing IL-6-induced inflammatory and angiogenic factors, their efficacy may differ owing to specific molecular mechanisms and pharmacological properties.