Zhang Qiwei, Seltmann Holger, Zouboulis Christos C, Travers Jeffrey B
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Exp Dermatol. 2006 Oct;15(10):769-74. doi: 10.1111/j.1600-0625.2006.00458.x.
Platelet-activating factor (PAF) is a group of phosphocholines with various biological effects mediated by the PAF receptor (PAF-R). Activation of the epidermal PAF-R induces the expression of inflammatory mediators, including cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). The upregulation of COX-2 expression has been shown to be involved in sebocyte proliferation, sebaceous gland inflammation and carcinogenesis. The present study was designed to investigate whether PAF-R activation could induce the expression of COX-2 and production of PGE(2), as well as secretion of the inflammatory cytokine, interleukin-8 (IL-8), in the immortalized sebaceous gland cell line SZ95. Using calcium mobilization studies, we first confirmed that PAF can signal through PAF-R in SZ95 sebocytes. We then found that the production of IL-8 was induced following treatment with PAF-R agonist, however blocked by a specific PAF-R antagonist. Induction of COX-2 expression and increased PGE(2) production were observed in SZ95 sebocytes after PAF-R activation. Finally, it was demonstrated that the production of PGE(2), induced by PAF-R activation and mediated by COX-2 expression, was blocked following PAF-R antagonism in SZ95 sebocytes. These studies suggest that SZ95 sebocytes express functional PAF-Rs and PAF-Rs are involved in regulating the expression of inflammatory mediators, including COX-2, PGE(2) and IL-8.
血小板活化因子（PAF）是一类磷酸胆碱，具有由PAF受体（PAF-R）介导的多种生物学效应。表皮PAF-R的激活可诱导炎症介质的表达，包括环氧合酶-2（COX-2）和前列腺素E2（PGE2）。COX-2表达的上调已被证明与皮脂细胞增殖、皮脂腺炎症和致癌作用有关。本研究旨在探讨PAF-R激活是否能诱导永生化皮脂腺细胞系SZ95中COX-2的表达、PGE2的产生以及炎症细胞因子白细胞介素-8（IL-8）的分泌。通过钙动员研究，我们首先证实PAF可通过SZ95皮脂细胞中的PAF-R发出信号。然后我们发现，用PAF-R激动剂处理后可诱导IL-8的产生，但被特异性PAF-R拮抗剂阻断。PAF-R激活后，在SZ95皮脂细胞中观察到COX-2表达的诱导和PGE2产生的增加。最后，证明在SZ95皮脂细胞中，PAF-R拮抗作用后，由PAF-R激活诱导并由COX-2表达介导的PGE2产生被阻断。这些研究表明，SZ95皮脂细胞表达功能性PAF-Rs，且PAF-Rs参与调节包括COX-2、PGE2和IL-8在内的炎症介质的表达。
