کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5843198 | 1560858 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Corticosteroids modulate the expression of the PKC-anchoring protein RACK-1 and cytokine release in THP-1 cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
TNFRACK-1ssDNAGRELSPTLRPKCIL-8single stranded DNA - DNA تک رشته ایinterferon - اینترفرونIFN - اینترفرون هاInterleukin-8 - اینترلوکین -8Toll-like receptor - تیالآرCytokines - سیتوکین هاglucocorticoid responsive element - عنصر واکنش گلوکوکورتیکوئیدtumor necrosis factor - فاکتور نکروز تومورlipopolysaccharide - لیپوپلی ساکاریدSignal transduction - هدایت سیگنالProtein kinase C - پروتئین کیناز سیCorticosteroids - کورتیکواستروئیدهاglucocorticoid receptor - گیرنده گلوکوکورتیکوئید
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
We demonstrated that cortisol reduces the expression of RACK-1 (Receptor for Activated C Kinase-1), a protein required for immune cell activation. The aim of this study was to evaluate whether and to what extent other clinically relevant corticosteroids may modulate RACK-1 expression.We used the human promyelocytic cell line THP-1 to investigate the effects of cortisol, prednisone, prednisolone, budesonide, betamethasone and methylprednisolone on RACK-1 expression and cytokine production. As anticipated, all corticosteroids inhibited at non-cytotoxic concentrations in a dose and time related manner LPS-induced TNF-α and IL-8 release, with budesonide, betamethasone and methylprednisolone being the most active followed by prednisolone, cortisol and prednisone. To a similar extent, all corticosteroids also reduced RACK-1 mRNA expression and RACK-1 protein levels as assessed by Real Time PCR and Western blot, respectively. Prednisone was the least potent compound while betamethasone and methylprednisolone where the most active. A good correlation was observed between RACK-1 mRNA or protein levels and cytokine release (Pearson r = 0.7376, p = 0.0471 for RACK-1 mRNA and TNF-α release, and Pearson r = 0.8108, p = 0.0252 for RACK-1 protein and IL-8 release).Mifepristone, a potent glucocorticoid receptor (GR) antagonist, completely prevented the effect of cortisol, demonstrating that RACK-1 downregulation is via GR. Furthermore, to by-pass the defective PKC activation due to the decrease in RACK-1, we used a RACK-1 pseudosubstrate, that directly activates PKC-beta. RACK-1 pseudosubstrate was able to restore LPS-induced cytokine production affected by cortisol, supporting the role of RACK-1 in the anti-inflammatory effect of corticosteroids.These results confirm the involvement of RACK-1 in immune cell activation and identify this protein as a novel transcriptional target of corticosteroid-induced anti-inflammatory effects.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 81, March 2014, Pages 10-16
Journal: Pharmacological Research - Volume 81, March 2014, Pages 10-16
نویسندگان
Emanuela Corsini, Antonella Pinto, Valentina Galbiati, Barbara Viviani, Corrado L. Galli, Marina Marinovich, Marco Racchi,