PDRN, a Bioactive Natural Compound, Ameliorates Imiquimod-Induced Psoriasis through NF-κB Pathway Inhibition and Wnt/β-Catenin Signaling Modulation.
Animals
Cytokines
/ metabolism
Disease Models, Animal
Imiquimod
/ adverse effects
Keratinocytes
/ metabolism
Mice
Mice, Inbred BALB C
NF-kappa B
/ metabolism
Polydeoxyribonucleotides
/ pharmacology
Psoriasis
/ chemically induced
Receptor, Adenosine A2A
/ metabolism
Skin
/ metabolism
Wnt Signaling Pathway
/ drug effects
beta Catenin
/ metabolism
NF-κB
Wnt/β-catenin pathway
adenosine A2A receptor
psoriasis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
12 Feb 2020
12 Feb 2020
Historique:
received:
08
01
2020
revised:
31
01
2020
accepted:
07
02
2020
entrez:
16
2
2020
pubmed:
16
2
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Nuclear factor-κB (NF-κB) plays a central role in psoriasis and canonical Wnt/β-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation blocks NF-κB and boosts the Wnt/β-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/β-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-κB inhibition and Wnt/β-catenin stimulation.
Identifiants
pubmed: 32059361
pii: ijms21041215
doi: 10.3390/ijms21041215
pmc: PMC7072802
pii:
doi:
Substances chimiques
Cytokines
0
NF-kappa B
0
Polydeoxyribonucleotides
0
Receptor, Adenosine A2A
0
beta Catenin
0
Imiquimod
P1QW714R7M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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