Reference - Detail
| RRC ID | 62986 |
|---|---|
| Author | Aota K, Yamanoi T, Kani K, Ono S, Momota Y, Azuma M. |
| Title | Inhibition of JAK-STAT Signaling by Baricitinib Reduces Interferon-γ-Induced CXCL10 Production in Human Salivary Gland Ductal Cells. |
| Journal | Inflammation |
| Abstract |
Sjögren'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. |
| Volume | 44(1) |
| Pages | 206-216 |
| Published | 2021-2-1 |
| DOI | 10.1007/s10753-020-01322-w |
| PII | 10.1007/s10753-020-01322-w |
| PMID | 32772240 |
| MeSH | Azetidines / pharmacology* Azetidines / therapeutic use Cell Line, Transformed Chemokine CXCL10 / antagonists & inhibitors* Chemokine CXCL10 / biosynthesis Female Humans Interferon-gamma / pharmacology* Janus Kinase 1 / antagonists & inhibitors* Janus Kinase 1 / biosynthesis Janus Kinase 2 / antagonists & inhibitors* Janus Kinase 2 / biosynthesis Jurkat Cells Purines / pharmacology* Purines / therapeutic use Pyrazoles / pharmacology* Pyrazoles / therapeutic use STAT1 Transcription Factor / antagonists & inhibitors* STAT1 Transcription Factor / biosynthesis Salivary Ducts / drug effects Salivary Ducts / metabolism* Signal Transduction / drug effects Signal Transduction / physiology Sjogren's Syndrome / drug therapy Sjogren's Syndrome / metabolism Sulfonamides / pharmacology* Sulfonamides / therapeutic use |
| IF | 3.212 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Jurkat |