LXRalpha enhances lipid synthesis in SZ95 sebocytes.
Differentiation of sebocytes is strongly associated with enhanced lipid synthesis and accumulation in the cells. Liver X receptors (LXRs) are members of the nuclear receptor superfamily, which play a critical role in cholesterol homeostasis and lipid metabolism. We examined whether LXRalpha regulated lipid synthesis in the immortalized human sebaceous gland cell line SZ95. When the SZ95 sebocytes were treated with the ligand of LXR such as TO901317 or 22(R)-hydroxycholesterol, lipid droplets were accumulated in the majority of cells when examined by Oil Red O staining. The expression of the known LXR targets, such as fatty acid synthase and sterol regulatory-binding protein-1, was induced by TO901317. TO901317 treatment increased expression of LXRalpha but not that of LXRbeta. Transfection of antisense LXRalpha significantly decreased TO901317-induced target gene expression and lipid droplet accumulation, suggesting a major role of LXRalpha in differentiation of sebocytes. Further, TO901317 decreased the expression of cyclooxygenase-2 and inducible nitric oxide synthase that was induced by lipopolysaccharide treatment. Together, these results indicate that important roles of LXRalpha in differentiation and inflammatory signaling in sebaceous glands. Thus, we suggest that LXR ligands could provide a new class of therapeutic agents for sebaceous gland-associated disorders such as seborrhea and acne.
Hong
Il
I
College of Pharmacy and Bio-MAX Institute, Seoul National University, Seoul, Korea.
Lee
Min-Ho
MH
Na
Tae-Young
TY
Zouboulis
Christos C
CC
Lee
Mi-Ock
MO
D001391:Azo Compounds; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D004396:Coloring Agents; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D012627:Sebaceous Glands / Q000166:cytology / Q000378:metabolism*; D012629:Sebum / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D014162:Transfection; D019014:fas Receptor / Q000235:genetics / Q000276:immunology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D001391:Azo Compounds; D004396:Coloring Agents; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D008055:Lipids; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D019014:fas Receptor; C000605213:NR1H3 protein, human; C497387:SREBF1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C011049:oil red O