Document Detail


Phytosphingosine stimulates the differentiation of human keratinocytes and inhibits TPA-induced inflammatory epidermal hyperplasia in hairless mouse skin.
MedLine Citation:
PMID:  16838068     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 PPARgamma 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, loricrin, and keratin1 were also increased in PS-treated NHEKs, by ELISA or Western blotting analysis. A [(3)H]thymidine incorporation assay showed that PS inhibited DNA synthesis in NHEKs 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 E(2) in peripheral mononuclear leukocytes. Taken together, our results provide 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.
Authors:
Sujong Kim; Il Hong; Jung Sun Hwang; Jin Kyu Choi; Ho Sik Rho; Duck Hee Kim; Ihseop Chang; Seung Hun Lee; Mi-Ock Lee; Jae Sung Hwang
Related Documents :
12175988 - Il-8-stimulated expression of urokinase-type plasminogen activator in human skin and hu...
16766888 - A new silver-loaded cellulosic fiber with antifungal and antibacterial properties.
15131578 - Expression of fractalkine and its receptor, cx3cr1, in atopic dermatitis: possible cont...
24626328 - Eosinophils are important for protection, immunoregulation and pathology during infecti...
22399378 - Sensing necrotic cells.
16320828 - Curcumin protects human chondrocytes from il-l1beta-induced inhibition of collagen type...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  12     ISSN:  1076-1551     ISO Abbreviation:  Mol. Med.     Publication Date:    2006 Jan-Mar
Date Detail:
Created Date:  2006-08-30     Completed Date:  2006-09-13     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-24     Citation Subset:  IM    
Affiliation:
Skin Research Institute, AmorePacific Corporation R&D Center, Yongin-si, Kyounggi, Korea. sundance@amorepacific.com
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Dinoprostone / biosynthesis,  secretion
Epidermis / cytology,  drug effects,  pathology*
Humans
Hyperplasia / drug therapy,  pathology*
Inflammation
Keratinocytes / cytology*,  drug effects*
Leukocytes, Mononuclear / drug effects
Male
Mice
Mice, Hairless
PPAR gamma / genetics
Peroxidase / metabolism
Sphingosine / analogs & derivatives*,  chemistry,  pharmacology
Tetradecanoylphorbol Acetate / antagonists & inhibitors,  pharmacology*
Transcription, Genetic / drug effects
Chemical
Reg. No./Substance:
0/PPAR gamma; 123-78-4/Sphingosine; 16561-29-8/Tetradecanoylphorbol Acetate; 363-24-6/Dinoprostone; 554-62-1/phytosphingosine; EC 1.11.1.7/Peroxidase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Peeling off the hidden genetic heterogeneities of cancers based on disease-relevant functional modul...
Next Document:  Selective inhibition of the human tie-1 promoter with triplex-forming oligonucleotides targeted to E...