کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815076 | 1058447 | 2016 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phosphodiesterase 4 in inflammatory diseases: Effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex
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کلمات کلیدی
IgMDLEIP-10IL1FACSGM-CSFIFN-γEGTADAPI4′,6-diamidino-2-phenylindole dihydrochloride - 4 '، 6-دی آمیدین-2-فنیلینول دی هیدروکلرایدBSA - BSAcAMP - cAMPDMSO - DMSOCyclic adenosine monophosphate - آدنوزین مونوفسفات Cyclicethylene glycol tetraacetic acid - اتیلن گلیکول تتراستیک اسیدgrowth-regulated oncogene - انکوزن تنظیم شده با رشدImmunohistochemistry - ایمونوهیستوشیمیIHC - ایمونوهیستوشیمیimmunoglobulin M - ایمونوگلوبولین Minterleukin 1 - اینترلوکین 1analysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceELISA - تست الیزاEnzyme-linked immunosorbent assay - تست الیزاAtopic dermatitis - درماتیت آتوپیکfluorescence-activated cell sorting - دسته بندی سلول های فعال فلورسنسDimethyl sulfoxide - دیمتیل سولفواکسیدbody surface area - سطح بدنgranulocyte-macrophage colony-stimulating factor - عامل گرانولوسیت-ماکروفاژ colony-stimulating factorgranulocyte colony-stimulating factor - فاکتور تحریک کننده کلنی گرانولوسیتG-CSF - فاکتور محرک کُلونی گرانولوسیتdermal fibroblasts - فیبروبلاست های پوستیdiscoid lupus erythematosus - لوپوس دیسویود erythematosusInterferon gamma - گاما اینترفرونGro - گور
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Phosphodiesterases 4 (PDE4) act as proinflammatory enzymes via degradation of cAMP, whereas PDE4 inhibitors play an anti-inflammatory role in vitro and in vivo. In particular, apremilast has been recently approved for the treatment of psoriasis and psoriatic arthritis. However, little is known on the expression pattern of PDE4 in psoriasis. We report that PDE4B and PDE4D mRNA are overexpressed in peripheral blood mononuclear cells (PBMC) from psoriasis, as compared with normal controls, while apremilast reduces PBMC production of a number of pro-inflammatory cytokines and increases the levels of anti-inflammatory mediators. PDE4 expression is up-regulated in psoriatic dermis as compared with normal skin, with particular regard to fibroblasts. This is confirmed in vitro, where both dermal fibroblasts (DF) and, to a greater extent, myofibroblasts (DM) express all PDE4 isoforms at the mRNA and protein level. Because PDE4 interacts with the nerve growth factor (NGF) receptor CD271 in lung fibroblasts, we evaluated the relationship and function of PDE4 and CD271 in normal human skin fibroblasts. All PDE4 isoforms co-immunoprecipitate with CD271 in DM, while apremilast inhibits apoptosis induced by β-amyloid, a CD271 ligand, in DM. Furthermore, apremilast significantly reduces NGF- and transforming growth factor-β1 (TGF-β1)-induced fibroblast migration, and inhibits DF differentiation into DM mediated by NGF or TGF-β1. Finally, in DM, apremilast significantly reduces cAMP degradation induced by treatment with β-amyloid. Taken together, these results indicate that PDE4 play an important role in psoriasis. In addition, the study reveals that the PDE4/CD271 complex could be important in modulating fibroblast functions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 28, Issue 7, July 2016, Pages 753-763
Journal: Cellular Signalling - Volume 28, Issue 7, July 2016, Pages 753-763
نویسندگان
Peter H. Schafer, Francesca Truzzi, Anastasia Parton, Lei Wu, Jolanta Kosek, Ling-Hua Zhang, Gerald Horan, Annalisa Saltari, Marika Quadri, Roberta Lotti, Alessandra Marconi, Carlo Pincelli,