PDRN, a Bioactive Natural Compound, Ameliorates Imiquimod-Induced Psoriasis through NF-κB Pathway Inhibition and Wnt/β-Catenin Signaling Modulation

被引：22

作者：

Irrera, Natasha ^{[1
]}

Bitto, Alessandra ^{[1
]}

Vaccaro, Mario ^{[1
]}

Mannino, Federica ^{[1
]}

Squadrito, Violetta ^{[1
]}

Pallio, Giovanni ^{[1
]}

Arcoraci, Vincenzo ^{[1
]}

Minutoli, Letteria ^{[1
]}

Ieni, Antonio ^{[2
]}

Lentini, Maria ^{[2
]}

Altavilla, Domenica ^{[3
]}

Squadrito, Francesco ^{[1
]}

机构：

[1] Univ Messina, Dept Clin & Expt Med, AOU Policlin G Martino, Via C Valeria Gazzi, I-98125 Messina, Italy

[2] Univ Messina, Dept Human Pathol Adult & Dev Age Gaetano Barresi, AOU Policlin G Martino, Via C Valeria Gazzi, I-98125 Messina, Italy

[3] Univ Messina, Dept Biomed & Dent Sci & Morphol & Funct Sci, AOU Policlin G Martino, Via C Valeria Gazzi, I-98125 Messina, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 04期

关键词：

adenosine A2A receptor; psoriasis; NF-kappa B; Wnt/beta-catenin pathway; ADENOSINE RECEPTOR STIMULATION; PATHOGENESIS; MECHANISMS;

D O I：

10.3390/ijms21041215

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nuclear factor-kappa B (NF-kappa B) plays a central role in psoriasis and canonical Wnt/beta-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation blocks NF-kappa B and boosts the Wnt/beta-catenin signaling. PDRN (Polydeoxyribonucleotide) is a biologic agonist of the A2A receptor and its effects were studied in an experimental model of psoriasis. Psoriasis-like lesions were induced by a daily application of imiquimod (IMQ) on the shaved back skin of mice for 7 days. Animals were randomly assigned to the following groups: Sham psoriasis challenged with Vaseline; IMQ animals challenged with imiquimod; and IMQ animals treated with PDRN (8 mg/kg/ip). An additional arm of IMQ animals was treated with PDRN plus istradefylline (KW6002; 25 mg/kg/ip) as an A2A antagonist. PDRN restored a normal skin architecture, whereas istradefylline abrogated PDRN positive effects, thus pointing out the mechanistic role of the A2A receptor. PDRN decreased pro-inflammatory cytokines, prompted Wnt signaling, reduced IL-2 and increased IL-10. PDRN also reverted the LPS repressed Wnt-1/beta-catenin in human keratinocytes and these effects were abolished by ZM241385, an A2A receptor antagonist. Finally, PDRN reduced CD3+ cells in superficial psoriatic dermis. PDRN anti-psoriasis potential may be linked to a "dual mode" of action: NF-kappa B inhibition and Wnt/beta-catenin stimulation.

引用

页数：14