کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5684945 | 1597922 | 2017 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
JAK-inhibitor tofacitinib suppresses interferon alfa production by plasmacytoid dendritic cells and inhibits arthrogenic and antiviral effects of interferon alfa
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کلمات کلیدی
Rheumatoid arthritis synovial fibroblastsIFNαTLRPBMCJanus kinase - کیناز جانوس pDCs - pDC هاRheumatoid arthritis - آرتریتروماتوئیدSTAT - آمارinterferon alpha - اینترفرون آلفاtoll like receptor - تلفات مانند گیرندهperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیplasmacytoid dendritic cells - سلولهای دندریتیک پلاسماسیتیوئیدcytomegalovirus - سیتومگالوویروسCMV - سیتومگالوویروسSystemic lupus erythematosus - لوپوس اریتماتوی سیستمیکSLE - لوپوس منتشر یا لوپوس اریتماتوس سیستمیکSignal transducer and activator of transcription - مبدل سیگنال و فعال کننده رونویسیHepatitis C virus - هپاتیت سیHCV - هپاتیت سیJAK - چگونه
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: JAK-inhibitor tofacitinib suppresses interferon alfa production by plasmacytoid dendritic cells and inhibits arthrogenic and antiviral effects of interferon alfa JAK-inhibitor tofacitinib suppresses interferon alfa production by plasmacytoid dendritic cells and inhibits arthrogenic and antiviral effects of interferon alfa](/preview/png/5684945.png)
چکیده انگلیسی
Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections. Using in vitro culture models with human cells, we studied the effects of tofacitinib on PDC survival and IFNα production, and on arthrogenic and antiviral effects of IFNα. Tofacitinib inhibited the expression of antiapoptotic BCL-A1 and BCL-XL in human PDC and induced PDC apoptosis. TLR7 stimulation upregulated the levels of antiapoptotic Bcl-2 family members and prevented the induction of PDC apoptosis by tofacitinib. However, tofacitinib robustly inhibited the production of IFNα by toll like receptor-stimulated PDC. In addition, tofacitinib profoundly suppressed IFNα-induced upregulation of TLR3 on synovial fibroblasts, thereby inhibiting their cytokine and protease production in response to TLR3 ligation. Finally, tofacitinib counteracted the suppressive effects of IFNα on viral replication. Tofacitinib inhibits PDC survival and IFNα production and suppresses arthrogenic and antiviral effects of IFNα signaling. Inhibition of the IFNα pathway at 2 levels may contribute to the beneficial effects of tofacitinib in autoimmune diseases and explain the increased viral infection rates observed during tofacitinib treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 188, October 2017, Pages 67-79
Journal: Translational Research - Volume 188, October 2017, Pages 67-79
نویسندگان
Patrick P.C. Boor, Petra E. de Ruiter, Patrick S. Asmawidjaja, Erik Lubberts, Luc J.W. van der Laan, Jaap Kwekkeboom,