التفاصيل البيبلوغرافية
| العنوان: |
Phytosphingosine Stimulates the Differentiation of Human Keratinocytes and Inhibits TPA-lnduced Inflammatory Epidermal Hyperplasia in Hairless Mouse Skin. |
| المؤلفون: |
Sujong Kim1, Il Hong2, Lung Sun Hwang1, Jin Kyu Choi1, Ho Sik Rho1, Duck Hee Kim1, Ihseop Chang1, Seung Hun Lee3, Mi-Ock Lee2, Jae Sung Hwang1 jshwang@amorepacific.com |
| المصدر: |
Molecular Medicine. Jan-Mar2006, Vol. 12 Issue 1-3, p17-24. 8p. 4 Color Photographs, 1 Diagram, 11 Graphs. |
| مصطلحات موضوعية: |
*PEROXISOMES, *KERATINOCYTES, *POLYMERASE chain reaction, *MESSENGER RNA, *ENZYME-linked immunosorbent assay, *WESTERN immunoblotting |
| مستخلص: |
The binding of sphingoid bases to peroxisome proliferator-activated receptor (PPAR) has been detected in a solid-phase binding assay. However, sphingoid base-induced changes in PPAR transactivation activity have not been examined. In this report, we show by reporter gene analyses that phytosphingosine (PS). a natural sphingoid base, activates the transcriptional activity of PPARs in the immortalized human keratinocyte, HaCaT. Real-time PCR analyses showed that the mRNA level of PPARγ was increased after PS treatment in HaCaT cells in a dose- and time-dependent manner. Because PPARs play important roles in skin barrier homeostasis by regulating epidermal cell growth, terminal differentiation, and inflammatory response, we examined the effect of PS on normal human epidermal keratinocytes (NHEKs) and mouse skin, PS increased the production of cornified envelope in NHEKs by approximately 1.8-fold compared with controls, Epidermal differentiation marker proteins such as involucrin, Ioricrin, and keratin1 were also increased in PS-treated NHEKs, by ELISA or Western blotting analysis. A (³H)thymidine incorporation assay showed that PS inhibited DNA synthesis in NHEK5 to 20% compared with controls. The antiproliferative and anti-inflammatory effects of PS were examined in a mouse model of irritant contact dermatitis produced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA). PS blocked epidermal thickening and edema and the infiltration of inflammatory cells into the dermis in the skin of TPA-treated hairless mice. The anti-inflammatory effects of PS were confirmed by the observation that PS blocked the TPA-induced generation of prostaglandin E2 in peripheral mononuclear leukocytes. Taken together, our results pro- vide an insight into the multiple regulatory roles of PS in epidermal homeostasis, and furthermore point to the potential use of PS as a therapeutic agent in the treatment of inflammatory and proliferative cutaneous diseases. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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