کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5843846 | 1127266 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
phosphorylated p38DTHTregTNFERKELISPOTIgEIgGPBMCJnkphosphorylated JNKLPSCMTc-Jun N-terminal kinases - C-Jun N-terminal kinasesPhosphorylated ERK - ERK فسفریلیت شدهMAPK - MAPKAllergic rhinoconjunctivitis - rhinoconjunctivitis آلرژیکrhinoconjunctivitis - rinoconjunctivitisAsthma - آسمAllergy - آلِرژیinterferon - اینترفرونIFN - اینترفرون هاinterleukin - اینترلوکینchemically modified tetracyclines - تتراسایکلین های اصلاح شده شیمیاییEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاDelayed type hypersensitivity - حساسیت نوع تاخیریAllergic rhinitis - رینیت آلرژیکRegulatory T cell - سلول T تنظیم کنندهCD4 T cells - سلول های CD4 TCD8 T cells - سلول های CD8 Tperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیPeripheral blood mononuclear cells (PBMC) - سلول های تک هسته ای خون محیطی (PBMC)Helper T cell - سلول کمک کنندهtumor necrosis factor - فاکتور نکروز تومورlipopolysaccharide - لیپوپلی ساکاریدMinocycline - مینوسایکلینLate phase response - پاسخ مرحلۀ بعدیmitogen activated protein kinase - پروتئین کیناز فعال Mitogen فعال استmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenMAP kinase - کیناز MAPextracellular signal-regulated kinases - کیناز های تنظیم شده سیگنال خارج سلولی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
All available therapies for human allergic disease target IgE mediated pathologic responses after IgE has been produced. We are developing tetracyclines as anti-allergy drugs to prevent IgE production, based on our findings that minocycline or doxycycline treatment of allergic asthmatic humans significantly improves their asthma symptoms, reduces their oral steroid requirements, and strongly suppresses their ongoing IgE responses (ELISA, mast cell mediated cutaneous late phase responses); the tetracyclines also strongly suppress peak IgE responses of BPO-KLH sensitized mice (ELISPOT assay, ELISA, skin tests). The antibiotic activity of the tetracyclines is not required for suppression of IgE responses; inclusion of minocycline or doxycycline in sterile culture prevents anti-CD40/IL-4 mediated induction of memory IgE responses by PBMC of allergic asthmatic patients (ELISA), and induction of specific memory IgE responses by spleen cells of BPO-KLH sensitized mice (ELISPOT assay, ELISA). The tetracyclines affect an epsilon specific pathway because IgM, IgG and IgA responses did not decrease. Further, in humans, DTH responses to recall antigens did not decrease. In related studies, we found that two distinct T cell subsets: CD4+CD60 negative and CD8+CD60+ (CD60 is a ganglioside) (humans) and CD4+ Asialo GM1 ganglioside negative and CD8+Asialo GM1 ganglioside+ (mice), both are required for induction of memory IgE responses. Phosphorylated (phos) p38 MAP kinase, but not phos ERK or phos JNK expression by CD4+ and CD8+, including CD8+CD60+, T cells is increased in allergic asthmatic humans, as is IL-4 and IL-10 production. The tetracyclines appear to target T cell pathways to induce suppression of IgE responses because they suppress phos p38 MAP kinase expression by both CD4+ and CD8+, including CD8+CD60+, T cell subsets, and IL-4 and IL-10, while upregulating IL-2 and IFN gamma, and suppressing IgE responses. Our finding that tetracyclines do not require antibiotic activity to suppress IgE responses opens the door to development of new tetracycline-based and other therapeutics for human allergic disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 64, Issue 6, December 2011, Pages 602-609
Journal: Pharmacological Research - Volume 64, Issue 6, December 2011, Pages 602-609
نویسندگان
Rauno Joks, Helen G. Durkin,