CXCL10型
STAT蛋白
JAK-STAT信号通路
STAT1
导管细胞
趋化因子
唾液腺
干扰素
细胞因子
免疫系统
贾纳斯激酶
信号转导
免疫学
癌症研究
内科学
医学
生物
车站3
免疫组织化学
细胞生物学
酪氨酸激酶
作者
Keiko Aota,Tomoko Yamanoi,Koichi Kani,Shinji Ono,Yukihiro Momota,Masayuki Azuma
出处
期刊:Inflammation
[Springer Science+Business Media]
日期:2020-08-09
卷期号:44 (1): 206-216
被引量:55
标识
DOI:10.1007/s10753-020-01322-w
摘要
Sjogren’s syndrome (SS) is a chronic autoimmune disease targeting salivary and lacrimal glands. C-X-C motif chemokine ligand 10 (CXCL10) expression is upregulated in lip salivary glands (LSGs) of primary SS (pSS) patients, and CXCL10 involved in SS pathogenesis via immune-cell accumulation. Moreover, interferon (IFN)-γ enhances CXCL10 production via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. We investigated the effects of baricitinib, a selective JAK1/2 inhibitor, on both IFN-γ-induced CXCL10 production and immune-cell chemotaxis. We used immunohistochemical staining to determine the expression levels and localization of JAK1 and JAK2 in LSGs of SS patients (n = 12) and healthy controls (n = 3). We then evaluated the effect of baricitinib in an immortalized normal human salivary gland ductal (NS-SV-DC) cell line. Immunohistochemical analysis of LSGs from pSS patients revealed strong JAK1 and JAK2 expression in ductal and acinar cells, respectively. Baricitinib significantly inhibited IFN-γ-induced CXCL10 expression as well as the protein levels in an immortalized human salivary gland ductal-cell clone in a dose-dependent manner. Additionally, western blot analysis showed that baricitinib suppressed the IFN-γ-induced phosphorylation of STAT1 and STAT3, with a stronger effect observed in the case of STAT1. It also inhibited IFN-γ-mediated chemotaxis of Jurkat T cells. These results suggested that baricitinib suppressed IFN-γ-induced CXCL10 expression and attenuated immune-cell chemotaxis by inhibiting JAK/STAT signaling, suggesting its potential as a therapeutic strategy for pSS.
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