Charlie Norwood VA Medical Center, Augusta, Georgia (V.C., W.B.B.); Institute of Molecular Medicine and Genetics, Department of Medicine (D.X., M.S., W.B.B.), Department of Physiology (D.X., V.C., M.S., A.W., A.C.E., K.A.B., W.B.B.), Department of Family Medicine (D.X.), Department of Neuroscience and Regenerative Medicine (M.H.J.), and Division of Dermatology, Department of Medicine (W.B.B.), Medical College of Georgia, Augusta University, Augusta, Georgia; and Apeliotus Technologies, Inc., Philadelphia, Pennsylvania (J.G.E., W.B.B.).
Charlie Norwood VA Medical Center, Augusta, Georgia (V.C., W.B.B.); Institute of Molecular Medicine and Genetics, Department of Medicine (D.X., M.S., W.B.B.), Department of Physiology (D.X., V.C., M.S., A.W., A.C.E., K.A.B., W.B.B.), Department of Family Medicine (D.X.), Department of Neuroscience and Regenerative Medicine (M.H.J.), and Division of Dermatology, Department of Medicine (W.B.B.), Medical College of Georgia, Augusta University, Augusta, Georgia; and Apeliotus Technologies, Inc., Philadelphia, Pennsylvania (J.G.E., W.B.B.)
J Pharmacol Exp Ther. 2018 Jul;366(1):1-8. doi: 10.1124/jpet.117.244756. Epub 2018 Apr 25.
We have previously shown that phosphatidylglycerol (PG) regulates the function of keratinocytes, the predominant cells that compose the epidermis, inhibiting the proliferation of rapidly dividing keratinocytes. In particular, soy PG, a PG mixture with a high proportion of polyunsaturated fatty acids, is efficacious at inhibiting these proliferating keratinocytes. Psoriasis is a skin disorder characterized by hyperproliferation of keratinocytes and inflammation. Data in the lung suggest that PG in pulmonary surfactant inhibits inflammation. To investigate the possibility of using PG containing polyunsaturated fatty acids for the treatment of psoriasis, we examined the effect of soy PG on inflammation induced by the application of 12--tetradecanoylphorbol 13-acetate (TPA), a contact irritant, to mouse ears in vivo. We monitored ear thickness and weight as a measure of ear edema, as well as CD45-positive immune cell infiltration. Our results indicate that soy PG when applied together with 1,25-dihydroxyvitamin D (vitamin D), an agent known to acutely disrupt the skin barrier, suppressed ear edema and inhibited the infiltration of CD45-positive immune cells. On the other hand, neither PG nor vitamin D alone was effective. The combination also decreased tumor necrosis factor- (TNF) levels. This result suggested the possibility that PG was not permeating the skin barrier efficiently. Therefore, in a further study we applied PG in a penetration-enhancing vehicle and found that it inhibited inflammation induced by the phorbol ester and decreased CD45-positive immune cell infiltration. Our results suggest the possibility of using soy PG as a topical treatment option for psoriasis.
我们之前已经表明，磷脂酰甘油（PG）调节角质形成细胞的功能，角质形成细胞是构成表皮的主要细胞，抑制快速分裂的角质形成细胞的增殖。特别是，富含多不饱和脂肪酸的大豆 PG 混合物在抑制这些增殖的角质形成细胞方面是有效的。银屑病是一种以角质形成细胞过度增殖和炎症为特征的皮肤疾病。肺部的数据表明，肺表面活性物质中的 PG 可抑制炎症。为了研究使用含有多不饱和脂肪酸的 PG 治疗银屑病的可能性，我们研究了大豆 PG 对应用 12-十四烷酰佛波醇 13-乙酸酯（TPA）（一种接触性刺激物）在体内诱导的炎症的影响，TPA 可引起小鼠耳部炎症。我们监测了耳朵厚度和重量作为耳水肿的指标，以及 CD45 阳性免疫细胞浸润。我们的结果表明，大豆 PG 与 1,25-二羟基维生素 D（维生素 D）一起应用，维生素 D 是一种已知可急性破坏皮肤屏障的药物，可抑制耳水肿并抑制 CD45 阳性免疫细胞浸润。另一方面，PG 或维生素 D 单独使用均无效。该组合还降低了肿瘤坏死因子-（TNF）水平。这一结果表明 PG 可能没有有效地穿透皮肤屏障。因此，在进一步的研究中，我们将 PG 应用于渗透增强剂载体中，发现它抑制了佛波醇酯诱导的炎症，并减少了 CD45 阳性免疫细胞的浸润。我们的结果表明，大豆 PG 有可能作为治疗银屑病的局部治疗选择。
