出版社：American Society for Biochemistry and Molecular Biology
摘要：Liver X receptors (LXRs) and peroxisome proliferator-activatedreceptors (PPARs) are potent regulators of keratinocyte proliferation,differentiation, and epidermal permeability barrier homeostasis.Cholesterol sulfotransferase type 2B isoform 1b (SULT2B1b) isa key enzyme in the synthesis of cholesterol sulfate (CS), acritical regulator of keratinocyte differentiation and desquamation,as well as a mediator of barrier homeostasis. In this study,we assessed the effect of activators of LXR, PPAR, PPARß/,and PPAR on SULT2B1b gene expression and enzyme activity incultured human keratinocytes (CHKs). Our results demonstratethat PPAR and LXR activators increase SULT2B1b mRNA levels,with the most dramatic effect (a 26-fold increase) induced bythe PPAR activator ciglitazone. Ciglitazone upregulates SULT2B1bmRNA in a dose- and time-dependent manner. Moreover, the stimulationof SULT2B1b gene expression by LXR and PPAR activators occursin both undifferentiated and differentiated CHKs. The upregulationof SULT2B1b mRNA by ciglitazone appears to occur at a transcriptionallevel, because the degradation of SULT2B1b is not acceleratedby ciglitazone. In addition, cycloheximide almost completelyblocks the ciglitazone-induced increase in SULT2B1b mRNA, suggestingthat the transcription of SULTB1b mRNA is dependent on new proteinsynthesis. Finally, LXR and PPAR activators also increased theactivity of cholesterol sulfotransferase.
Thus, LXR and PPAR activators regulate the expression of SULT2B1b,the key enzyme in the synthesis of CS, which is a potent regulatorof epidermal differentiation and corneocyte desquamation.Abbreviations: CHK, cultured human keratinocyte; CS, cholesterol sulfate; CSTase, cholesterol sulfotransferase; LXR, liver X receptor; 25-OH, 25-hydroxycholesterol; PPAR, peroxisome proliferator-activated receptor; 22R, 22(R)-hydroxycholesterol; RAR, retinoic acid receptor; RXR, retinoid X receptor; SC, stratum corneum; SULT2B1b, cholesterol sulfotransferase type 2B isoform 1b
Supplementary key words cholesterol sulfate • liver X receptor • peroxisome proliferator-activated receptor //
, PPARß/
, and PPAR
on SULT2B1b gene expression and enzyme activity in cultured human keratinocytes (CHKs). Our results demonstrate that PPAR and LXR activators increase SULT2B1b mRNA levels, with the most dramatic effect (a 26-fold increase) induced by the PPAR
