Schiattarella Maria, Caiazzo Giuseppina, Di Caprio Roberta, Lembo Serena, Raimondo Annunziata, Ayala Fabio, Balato Nicola, Monfrecola Giuseppe, Fortunato Giuliana, Balato Anna
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
G Ital Dermatol Venereol. 2019 Apr;154(2):192-196. doi: 10.23736/S0392-0488.17.05537-7. Epub 2017 May 16.
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.
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.
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.
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.
大量报告表明，银屑病患者更容易发生脂蛋白过氧化，且对氧磷酶（PON）1（一种抗氧化和抗炎酶）的活性降低。因此，有人提出抗氧化系统功能失调和活性氧产生增加会引发免疫炎症事件，导致银屑病患者皮肤细胞逐渐受损。PON蛋白家族包括PON1、PON2和PON3，是对抗氧化应激最重要的内源性防御机制之一。在本研究中，我们调查了银屑病中PON基因表达情况以及皮肤氧化应激情况。
研究人群包括10例中重度斑块状银屑病患者和15例接受整形手术的健康供者作为对照。对银屑病皮损和非皮损皮肤进行皮肤打孔活检，以分析PON2和PON3基因表达。此外，还对离体全层健康皮肤器官培养物进行了氧化测定。
与健康对照相比，银屑病皮损和非皮损皮肤中PON2和PON3基因表达无显著差异。H2O2处理导致离体全层健康皮肤器官培养物中PON2和PON3表达显著降低；相反，用抗氧化剂N-乙酰-L-半胱氨酸（NAC）预处理样品则导致显著增加。有趣的是，用IL-17刺激离体全层健康皮肤器官培养物时，PON2和PON3表达未报告有显著变化。
综合我们的研究结果表明，在银屑病皮肤和离体实验模型中，强大的促氧化活性均未被内源性抗氧化机制有效对抗。
