Psoriasis: crucial role of LXR-α RNomics

Abstract

Liver X receptor-alpha (LXR-a), being a member of the nuclear receptor/transcription factor family, has been widely recognized to have a pleiotropic effect in the regulation of genes involved in innate immunity, inflammation and cholesterol homeostasis. Keeping in view the fact that psoriasis is a chronic, inflammatory and autoimmune disease with a high turnover of keratinocytes, this study was addressed to understand the functional RNomics of the LXR-a gene in cultured primary keratinocytes derived from skin biopsies of human psoriatic lesions, and from symptomless skin of psoriatic patients and clinically healthy subjects. The results of this study revealed for the first time that the LXR-a gene has an inherent capacity to regulate genes coding for inflammatory cytokines, cell cycle, immunomodulation and reactive oxygen species scavenging within human keratinocytes. Moreover, LXR-a gene knockdown within normal human keratinocytes simulated the genomic profile observed in psoriatic skin lesions. On the basis of our study, we propose that restoration of LXR-a expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin.

Modulation of LXR-α and the effector genes by Ascorbic acid and Statins in psoriatic keratinocytes

“…Semi-quantitative RT-PCR was used to determine the transcriptional expression of LXR-a, as well as its effecter genes Vitamin D receptor and Catalase using specific primers [4]. PCR reaction products were resolved on 2 % ethidium bromidestained agarose gels followed by densitometric scanning of each band on the gel.…”

“…Keratinocytes derived from skin biopsies from the clinically healthy subjects were carried out in Keratinocytes-Specific Media containing no antibiotic in 24-well plate [4]. The treatment with Atorvastatin (Sigma, PZ0001-5MG) ?22R hydroxycholestrol (Sigma, H9384-1MG) and Ascorbic acid (Sigma, A5960) ?22R hydroxycholestrol was performed.…”

“…Total cellular RNA was extracted using Trizol Reagent (Ambion) from the cells harvested at 48 h after the cellular transfection experiments, and the RNA yield and purity were determined spectrophotometrically [4] cDNA was synthesized from the extracted RNA. Semi-quantitative RT-PCR was used to determine the transcriptional expression of LXR-a, as well as its effecter genes Vitamin D receptor and Catalase using specific primers [4].…”

“…In our previous study, we have showed for the first time that LXR-a expression/function within psoriatic lesion may help in the switch over transition from psoriatic to symptomless skin. Changes in the expression of this receptor in skin-diseased conditions make it a candidate gene worthy of further investigation [4]. In the present study, we characterize the effect of alteration in expression of LXR-a in the skin leads to different pathological skin conditions like psoriasis.…”

“…Nuclear receptors LXR-a (Liver X Receptor-alpha, NR1H3) [1][2][3][4] is the master regulators of body cholesterol and control its intestinal absorption, reverse transport, and liver metabolism [5][6][7]. It is known to heterodimerize with Retinoid X Receptor and, upon ligand binding, stimulates the expression of target genes.…”