Suda Yoshihito, Ikuta Kemmei, Hayashi Shinya, Wada Kensuke, Anjiki Kensuke, Kamenaga Tomoyuki, Tsubosaka Masanori, Kuroda Yuichi, Nakano Naoki, Maeda Toshihisa, Tsumiyama Ken, Matsumoto Tomoyuki, Kuroda Ryosuke, Matsubara Tsukasa
Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki- Cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
Department of Orthopedic Surgery, Matsubara Mayflower Hospital, 944-25, Fujita, Katō, Hyogo, 944-25, Japan.
Sci Rep. 2025 Mar 21;15(1):9736. doi: 10.1038/s41598-025-94894-2.
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.
类风湿性关节炎（RA）涉及滑膜组织增殖、炎症和血管生成，并导致关节破坏。血管生成是治疗RA的关键治疗靶点，而Janus激酶（JAK）抑制剂已成为一种有前景的治疗方法。在本研究中，我们比较了五种JAK抑制剂，包括托法替布（TOF）、巴瑞替尼、培非替尼、乌帕替尼和非戈替尼，对RA滑膜组织中白细胞介素（IL）-6诱导的炎症的抑制作用。所有五种抑制剂均通过抑制信号转导子和转录激活子（STAT）1和STAT3的磷酸化，有效抑制IL-6诱导的炎症和血管生成因子，包括血管内皮生长因子、细胞间黏附分子-1和血管细胞黏附分子-1。总体而言，结果表明，虽然所有五种JAK抑制剂在减少IL-6诱导的炎症和血管生成因子方面均有效，但由于特定的分子机制和药理特性，它们的疗效可能有所不同。
