Department of Medicine, Jagiellonian University Medical College, 8 Skawinska Str., 31-066, Krakow, Poland.
Br J Dermatol. 2015 Feb;172(2):337-44. doi: 10.1111/bjd.13225. Epub 2014 Nov 30.
Pro- and anti-inflammatory metabolites of arachidonic acid - eicosanoids - participate in skin homeostasis, affecting the growth and differentiation of keratinocytes. Alterations of 12-lipoxygenase (LOX) and 15-LOX and their metabolites have been described in the epidermis of patients with psoriasis, but systemic production of 12-LOX and 15-LOX eicosanoids has not been studied in the disease.
To ascertain the frequencies of the genetic variants ALOX12 rs1126667 and ALOX15 rs11568070 in cases and controls, and to compare urinary metabolites of 12(S)-hydroxyeicosatetraenoic acid (HETE) between patients with psoriasis and healthy controls.
Patients with psoriasis (n = 200) were stratified depending on the severity of their dermal lesions. Genotyping was performed using a 5'-nuclease real-time assay. The concentrations of 12(S)-HETE, its metabolites and 15(S)-HETE were determined in urine samples using high-performance liquid chromatography-tandem mass spectrometry.
Tetranor-12(S)-HETE metabolite excretion was significantly higher in urine of patients with psoriasis, while excretion of 12(S)-HETE was decreased. Neither 12(S)-HETE nor tetranor-12(S)-HETE correlated with the type of disease or severity score. No difference in urinary 15(S)-HETE was found between the study groups. Genotype distribution of the ALOX12 rs1126667 or ALOX15 rs11568070 polymorphisms did not discriminate for the disease or its severity.
Systemic metabolism of 12(S)-HETE is accelerated in psoriasis because excretion of the tetranor-12(S)-HETE inactivation product is elevated. No correlation with the severity or extent of psoriasis is detectable. We propose that in patients with psoriasis, 12(S)-HETE to tetranor-12(S)-HETE conversion could be at least a marker for this disease, in which inflammation of the skin can induce microsomal beta-oxidation of this eicosanoid.
花生四烯酸的促炎和抗炎代谢物 - 类二十烷酸 - 参与皮肤稳态，影响角质形成细胞的生长和分化。在银屑病患者的表皮中已经描述了 12-脂氧合酶（LOX）和 15-LOX 及其代谢物的改变，但是尚未在该疾病中研究全身性 12-LOX 和 15-LOX 类二十烷酸的产生。
确定病例和对照中 ALOX12 rs1126667 和 ALOX15 rs11568070 遗传变异的频率，并比较银屑病患者和健康对照者尿 12(S)-羟基二十碳四烯酸（HETE）的代谢物。
根据皮肤病变的严重程度对银屑病患者进行分层。使用 5'-核酸酶实时测定法进行基因分型。使用高效液相色谱-串联质谱法测定尿样中 12(S)-HETE、其代谢物和 15(S)-HETE 的浓度。
银屑病患者尿液中四氢-12(S)-HETE 代谢产物的排泄明显增加，而 12(S)-HETE 的排泄减少。12(S)-HETE 或四氢-12(S)-HETE 均与疾病类型或严重程度评分无关。研究组之间尿液中 15(S)-HETE 无差异。ALOX12 rs1126667 或 ALOX15 rs11568070 多态性的基因型分布不能区分疾病或其严重程度。
银屑病患者中 12(S)-HETE 的全身代谢加速，因为四氢-12(S)-HETE 失活产物的排泄增加。与银屑病的严重程度或范围没有相关性。我们提出，在银屑病患者中，12(S)-HETE 至四氢-12(S)-HETE 的转化至少可以作为该疾病的标志物，其中皮肤炎症可以诱导这种类二十烷酸的微粒体β-氧化。
