The Janus kinase inhibitor (baricitinib) suppresses the rheumatoid arthritis active marker gliostatin/thymidine phosphorylase in human fibroblast-like synoviocytes

被引:4
作者
Joyo, Yuji [1 ,2 ]
Kawaguchi, Yohei [2 ,3 ]
Yonezu, Hiroki [2 ]
Senda, Hiroya [1 ]
Yasuma, Sanshiro [1 ]
Shiraga, Hiroo [1 ]
Nozaki, Masahiro [2 ]
Aoyama, Mineyoshi [4 ]
Asai, Kiyofumi [3 ]
Murakami, Hideki [2 ]
Waguri-Nagaya, Yuko [1 ]
机构
[1] Nagoya City Univ, Dept Orthopaed Surg, East Med Ctr, Chikusa Ku, Wakamizu 1, Nagoya, Aichi 4648547, Japan
[2] Nagoya City Univ, Dept Orthopaed Surg, Grad Sch Med Sci, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[3] Nagoya City Univ, Dept Glial Cell Biol, Grad Sch Med Sci, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[4] Nagoya City Univ, Dept Pathobiol, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan
关键词
Baricitinib; Fibroblast-like synoviocytes; Gliostatin/thymidine phosphorylase; Interferon gamma; Janus kinase; Rheumatoid arthritis; CELL GROWTH-FACTOR; INTERFERON-GAMMA; THYMIDINE PHOSPHORYLASE; NEUROTROPHIC ACTION; EXPRESSION; MECHANISMS; INDUCTION; CYTOKINES; NEURONS;
D O I
10.1007/s12026-022-09261-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities in the pathogenesis of rheumatoid arthritis (RA). The novel oral Janus kinase (JAK) inhibitor baricitinib has demonstrated high efficacy in RA. However, the effect of baricitinib on fibroblast-like synoviocytes (FLSs), a key component of invasive synovitis, has not been still elucidated. This study investigated whether GLS/TP production could be regulated by JAK/signal transducers and activators of transcription (STAT) signaling in FLSs derived from patients with RA. FLSs were cultured and stimulated by interferon (IFN)gamma in the presence of baricitinib. Expression levels of GLS/TP were determined using reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunocytochemistry. Phosphorylation of STAT proteins was investigated by Western blot. In cultured FLSs, GLS/TP mRNA and protein levels were significantly induced by treatment with IFN gamma and these inductions were suppressed by baricitinib treatment. Baricitinib inhibited IFN gamma-induced STAT1 phosphorylation, while JAK/STAT activation played a pivotal role in IFN gamma-mediated GLS/ TP upregulation in RA. These results suggested that baricitinib suppressed IFN gamma-induced GLS/TP expression by inhibiting JAK/STAT signaling, resulting in the attenuation of neovascularization, synovial inflammation, and cartilage destruction.
引用
收藏
页码:208 / 215
页数:8
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