过氧化物酶增殖物激活受体β/δ在银屑病角质形成细胞中的表达

Expression of peroxisome proliferator-activated receptor β/δ in psoriatic epidermal keratinocytes

目的 探讨过氧化物酶增殖物激活受体β/δ （PPARβ/δ）在银屑病患者表皮角质形成细胞（KC）中的表达和调节因素.方法 免疫组化方法检测PPARβ/δ在银屑病患者皮损及非皮损表皮中的表达.分离、培养银屑病患者非皮损区和皮损区的KC,以RT-PCR和Western印迹法分别检测银屑病患者皮损区和非皮损区KC中PPARβ/δ mRNA和蛋白质的表达水平.利用PPARβ/δ外源性激动剂GW501516及Ca2＋刺激银屑病非皮损区KC,观察其对PPARβ/δ表达的调节影响.结果 免疫组化显示,银屑病皮损区PPARβ/δ的表达强度显著高于正常对照组（t=19.28,P＜0.01）和非皮损区（t=23.26,P＜0.01）.银屑病皮损区PPARβ/δ mRNA和蛋白质的表达水平均高于正常对照组（P＜0.01）和非皮损区（P＜ 0.01）.10 ng/ml GW501516最大效能促进PPARβ/δ的表达（P＜ 0.01）;1.0 mmol/L Ca2＋对KC中PPARβ/δ的表达促进效应最明显（P＜0.01）.结论 PPARβ/δ在银屑病患者皮损区表达显著升高,GW501516和CaCa2＋能够促进角质形成细胞PPARβ/δ表达水平.

Objective To measure the expression of peroxisome proliferator-activated receptor β/δ （PPARβ/δ） in epidermal keratinocytes from patients with psoriasis,and to investigate its regulatory factors.Methods Tissue specimens were obtained from both lesional and non-lesional skin of 20 patients with psoriasis as well as from normal skin of 15 human controls.An immunohistochemical method was used to examine the expression of PPARβ/δ in these tissue specimens.Epidermal keratinocytes were isolated from these tissue specimens and subjected to a primary culture.After several passages of subculture,non-lesional psoriatic keratinocytes were stimulated with different concentrations of GW501516 （an agonist of PPARβ/δ,0-100 ng/ml） and Ca2＋ （0-3.0 mmol/L）.Reverse transcription-PCR and Western blot were performed to measure the mRNA and protein expressions of PPARβ/δ in the primary keratinocytes and stimulated keratinocytes respectively.Results Immunohistochemistry showed that the expression intensity of PPARβ/δ was significantly higher in lesional psoriatic skin than in normal control skin （t =19.28,P ＜ 0.01） and non-lesional psoriatic skin （t =23.26,P ＜ 0.01）.Increased mRNA and protein levels of PPARβ/δ were observed in lesional psoriatic keratinocytes as compared to normal control keratinocytes （both P ＜0.01） and non-lesional psoriatic keratinocytes （both P ＜ 0.01）.Among these stimulated non-lesional psoriatic keratinocytes,those treated with GW501516 at 10 ng/ml and those with Ca2＋ of 1.0 mmol/L showed the strongest expression of PPARβ/δ （both P ＜ 0.01）.Conclusions The expression of PPARβ/δ,which is higher in lesional psoriatic skin,can be enhanced by GW501516 and Ca2＋ in keratinocytes.