کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5654869 | 1589410 | 2017 | 44 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
FBSPIADTHeffector memory T cellTEM cellCentral memory T cellpristane-induced arthritis - آرتروز ناشی از پرستانهRheumatoid arthritis - آرتریتروماتوئیدdelayed-type hypersensitivity - تاخیر نوع حساسیت بالاImmunomodulation - تنظیم ایمنی fetal bovine serum - سرم جنین گاوpolyethylene glycol - پلی اتیلن گلیکولPEG - پلیاتیلن گلیکول Voltage-gated channel - کانال ولتاژ
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog](/preview/png/5654869.png)
چکیده انگلیسی
Effector memory T lymphocytes (TEM cells) that lack expression of CCR7 are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. The Kv1.3 potassium channel is a key regulator of CCR7â TEM cell activation. Blocking Kv1.3 inhibits TEM cell activation and attenuates inflammation in autoimmunity, and as such, Kv1.3 has emerged as a promising target for the treatment of TEM cell-mediated autoimmune diseases. The scorpion venom-derived peptide HsTX1 and its analog HsTX1[R14A] are potent Kv1.3 blockers and HsTX1[R14A] is selective for Kv1.3 over closely-related Kv1 channels. PEGylation of HsTX1[R14A] to create a Kv1.3 blocker with a long circulating half-life reduced its affinity but not its selectivity for Kv1.3, dramatically reduced its adsorption to inert surfaces, and enhanced its circulating half-life in rats. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7â TEM cell proliferation, leaving CCR7+ naïve and central memory T cells able to proliferate. It reduced inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduced inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM cell-mediated autoimmune diseases. PEG-HsTX1[R14A] has the additional advantages of reduced non-specific adsorption to inert surfaces and enhanced circulating half-life.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Immunology - Volume 180, July 2017, Pages 45-57
Journal: Clinical Immunology - Volume 180, July 2017, Pages 45-57
نویسندگان
Mark R. Tanner, Rajeev B. Tajhya, Redwan Huq, Elizabeth J. Gehrmann, Kathia E. Rodarte, Mustafa A. Atik, Raymond S. Norton, Michael W. Pennington, Christine Beeton,