Paraoxonases and Psoriasis: Negative Imbalance of Antioxidant Endogenous Mechanisms

G Ital Dermatol Venereol. 2019 Apr;154(2):192-196. doi: 10.23736/S0392-0488.17.05537-7. Epub 2017 May 16.

Abstract

Background: Numerous reports have shown that psoriasis patients are more exposed to lipoprotein peroxidation and to a decrease in the activity of paraoxonase (PON)1, an antioxidant and anti-inflammatory enzyme. Thus, it has been suggested that malfunction of the antioxidant system and an increased production of reactive oxygen species drive immune inflammatory events, that result in progressive skin cell damage in patients with psoriasis. The PON protein family, including PON1, PON2 and PON3, is one of the most important endogenous defense mechanisms against oxidative stress. In the present study, we investigated PON gene expression in psoriasis and in cutaneous oxidative stress.

Methods: The study population included 10 patients affected by moderate-to-severe plaque psoriasis and 15 healthy donors who have undergone to plastic surgery, were used as control. Skin punch biopsies of lesional and non lesional psoriatic skin were performed for analysis of PON2 and PON3 gene expression. In addition, oxidation assays in ex vivo full-thickness healthy skin organ cultures were performed.

Results: No significant differences were observed between PON2 and PON3 gene expression in psoriatic lesional and non lesional skin compared with healthy controls. H2O2 treatment induced a significant decrease of PON2 and PON3 expression in ex vivo full-thickness healthy skin organ cultures; conversely the pretreatment of samples with the antioxidant reagent N-acetyl-L-cysteine (NAC) induced a significant increase. Interestingly, no significant alterations were reported for PON2 and PON3 expression in ex vivo full-thickness healthy skin organ cultures stimulated with IL-17.

Conclusions: Taken together our findings have revealed that a strong pro-oxidative activity is not effectively countered by antioxidant endogenous mechanisms both in psoriatic skin and in ex vivo experimental model.

MeSH terms

  • Acetylcysteine / pharmacology
  • Adult
  • Antioxidants / metabolism*
  • Aryldialkylphosphatase / genetics*
  • Case-Control Studies
  • Female
  • Gene Expression Regulation
  • Humans
  • Hydrogen Peroxide / administration & dosage
  • Male
  • Middle Aged
  • Oxidative Stress / genetics*
  • Psoriasis / enzymology
  • Psoriasis / genetics
  • Psoriasis / pathology*
  • Severity of Illness Index

Substances

  • Antioxidants
  • Hydrogen Peroxide
  • Aryldialkylphosphatase
  • PON2 protein, human
  • PON3 protein, human
  • Acetylcysteine