Bioactive dietary VDR ligands regulate genes encoding biomarkers of skin repair that are associated with risk for psoriasis

Amitis Karrys, Islam Rady, Roxane Cherille N. Chamcheu, Marya S. Sabir, Sanchita Mallick, Jean Christopher Chamcheu, Peter Jurutka, Mark R. Haussler, G. Kerr Whitfield

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Treatment with 1,25-dihydroxyvitamin D3 (1,25D) improves psoriasis symptoms, possibly by inducing the expression of late cornified envelope (LCE)3 genes involved in skin repair. In psoriasis patients, the majority of whom harbor genomic deletion of LCE3B and LCE3C (LCE3C_LCE3B-del), we propose that certain dietary analogues of 1,25D activate the expression of residual LCE3A/LCE3D/LCE3E genes to compensate for the loss of LCE3B/LCE3C in the deletant genotype. Herein, human keratinocytes (HEKn) homozygous for LCE3C_LCE3B-del were treated with docosahexaenoic acid (DHA) and curcumin, two low-affinity, nutrient ligands for the vitamin D receptor (VDR). DHA and curcumin induce the expression of LCE3A/LCE3D/LCE3E mRNAs at concentrations corresponding to their affinity for VDR. Moreover, immunohistochemical quantitation revealed that the treatment of keratinocytes with DHA or curcumin stimulates LCE3 protein expression, while simultaneously opposing the tumor necrosis factor-alpha (TNFα)-signaled phosphorylation of mitogen activated protein (MAP) kinases, p38 and Jun amino-terminal kinase (JNK), thereby overcoming inflammation biomarkers elicited by TNFα challenge. Finally, DHA and curcumin modulate two transcription factors relevant to psoriatic inflammation, the activator protein-1 factor Jun B and the nuclear receptor NR4A2/NURR1, that is implicated as a mediator of VDR ligand-triggered gene control. These findings provide insights into the mechanism(s) whereby dietary VDR ligands alter inflammatory and barrier functions relevant to skin repair, and may provide a molecular basis for improved treatments for mild/moderate psoriasis.

Original languageEnglish (US)
Article number174
JournalNutrients
Volume10
Issue number2
DOIs
StatePublished - Feb 4 2018

Fingerprint

psoriasis
Calcitriol Receptors
Curcumin
Docosahexaenoic Acids
vitamin D
Psoriasis
skin (animal)
curcumin
biomarkers
docosahexaenoic acid
Biomarkers
Ligands
Skin
receptors
Calcitriol
calcitriol
Keratinocytes
Genes
keratinocytes
Nuclear Receptor Subfamily 4, Group A, Member 2

Keywords

  • Activator protein-1
  • Curcumin
  • Differentiation
  • Docosahexaenoic acid
  • Epidermis
  • Keratinocytes
  • Late cornified envelope genes
  • Nutraceuticals
  • Psoriasis treatment
  • Vitamin D receptor

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Karrys, A., Rady, I., Chamcheu, R. C. N., Sabir, M. S., Mallick, S., Chamcheu, J. C., ... Whitfield, G. K. (2018). Bioactive dietary VDR ligands regulate genes encoding biomarkers of skin repair that are associated with risk for psoriasis. Nutrients, 10(2), [174]. https://doi.org/10.3390/nu10020174

Bioactive dietary VDR ligands regulate genes encoding biomarkers of skin repair that are associated with risk for psoriasis. / Karrys, Amitis; Rady, Islam; Chamcheu, Roxane Cherille N.; Sabir, Marya S.; Mallick, Sanchita; Chamcheu, Jean Christopher; Jurutka, Peter; Haussler, Mark R.; Whitfield, G. Kerr.

In: Nutrients, Vol. 10, No. 2, 174, 04.02.2018.

Research output: Contribution to journalArticle

Karrys, A, Rady, I, Chamcheu, RCN, Sabir, MS, Mallick, S, Chamcheu, JC, Jurutka, P, Haussler, MR & Whitfield, GK 2018, 'Bioactive dietary VDR ligands regulate genes encoding biomarkers of skin repair that are associated with risk for psoriasis', Nutrients, vol. 10, no. 2, 174. https://doi.org/10.3390/nu10020174
Karrys, Amitis ; Rady, Islam ; Chamcheu, Roxane Cherille N. ; Sabir, Marya S. ; Mallick, Sanchita ; Chamcheu, Jean Christopher ; Jurutka, Peter ; Haussler, Mark R. ; Whitfield, G. Kerr. / Bioactive dietary VDR ligands regulate genes encoding biomarkers of skin repair that are associated with risk for psoriasis. In: Nutrients. 2018 ; Vol. 10, No. 2.
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abstract = "Treatment with 1,25-dihydroxyvitamin D3 (1,25D) improves psoriasis symptoms, possibly by inducing the expression of late cornified envelope (LCE)3 genes involved in skin repair. In psoriasis patients, the majority of whom harbor genomic deletion of LCE3B and LCE3C (LCE3C_LCE3B-del), we propose that certain dietary analogues of 1,25D activate the expression of residual LCE3A/LCE3D/LCE3E genes to compensate for the loss of LCE3B/LCE3C in the deletant genotype. Herein, human keratinocytes (HEKn) homozygous for LCE3C_LCE3B-del were treated with docosahexaenoic acid (DHA) and curcumin, two low-affinity, nutrient ligands for the vitamin D receptor (VDR). DHA and curcumin induce the expression of LCE3A/LCE3D/LCE3E mRNAs at concentrations corresponding to their affinity for VDR. Moreover, immunohistochemical quantitation revealed that the treatment of keratinocytes with DHA or curcumin stimulates LCE3 protein expression, while simultaneously opposing the tumor necrosis factor-alpha (TNFα)-signaled phosphorylation of mitogen activated protein (MAP) kinases, p38 and Jun amino-terminal kinase (JNK), thereby overcoming inflammation biomarkers elicited by TNFα challenge. Finally, DHA and curcumin modulate two transcription factors relevant to psoriatic inflammation, the activator protein-1 factor Jun B and the nuclear receptor NR4A2/NURR1, that is implicated as a mediator of VDR ligand-triggered gene control. These findings provide insights into the mechanism(s) whereby dietary VDR ligands alter inflammatory and barrier functions relevant to skin repair, and may provide a molecular basis for improved treatments for mild/moderate psoriasis.",
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