کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8716105 | 1587878 | 2018 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The N-Acylethanolamine Acid Amidase Inhibitor ARN077 Suppresses Inflammation and Pruritus in a Mouse Model of Allergic Dermatitis
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موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
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چکیده انگلیسی
N-acylethanolamine acid amidase (NAAA), a cysteine hydrolase highly expressed in macrophages and B lymphocytes, catalyzes the degradation of palmitoylethanolamide. Palmitoylethanolamide is an agonist of PPAR-α and an important regulator of pain and innate immunity. In this study, we investigated the properties of the NAAA inhibitor, ARN077, in a mouse model of allergic contact dermatitis. Acute topical applications of ARN077 attenuated key signs of DNFB-induced dermatitis in a dose-dependent manner. Moreover, ARN077 increased tissue palmitoylethanolamide content and normalized circulating levels of cytokines and immunoglobulin E. No such effect was seen in PPAR-α-deficient mice. Moreover, mice lacking NAAA failed to develop edema or scratching behavior after challenge with DNFB, confirming that this enzyme plays an important role in dermatitis. Consistent with this conclusion, subchronic applications of ARN077 suppressed DNFB-induced inflammation when administered either before or after the DNFB challenge. The effects of subchronic ARN077 were dose dependent and comparable in size to those produced by the steroids clobetasol and dexamethasone. Unlike the latter, however, ARN077 did not cause skin atrophy. The results identify NAAA as a promising target for the development of effective and safe treatments for atopic dermatitis and other inflammatory disorders of the skin.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 3, March 2018, Pages 562-569
Journal: Journal of Investigative Dermatology - Volume 138, Issue 3, March 2018, Pages 562-569
نویسندگان
Oscar Sasso, Maria Summa, Andrea Armirotti, Silvia Pontis, Claudia De Mei, Daniele Piomelli,