@article{32dc72dc98e345ce909b4734edd814fa,
title = "Bioactive dietary VDR ligands regulate genes encoding biomarkers of skin repair that are associated with risk for psoriasis",
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.",
keywords = "Activator protein-1, Curcumin, Differentiation, Docosahexaenoic acid, Epidermis, Keratinocytes, Late cornified envelope genes, Nutraceuticals, Psoriasis treatment, Vitamin D receptor",
author = "Amitis Karrys and Islam Rady and Chamcheu, {Roxane Cherille N.} and Sabir, {Marya S.} and Sanchita Mallick and Chamcheu, {Jean Christopher} and Peter Jurutka and Haussler, {Mark R.} and Whitfield, {G. Kerr}",
note = "Funding Information: School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA; tkarrys12@gmail.com Department of Basic Medical Sciences, University of Arizona College of Medicine–Phoenix, Phoenix, AZ 85004, USA; peter.jurutka@asu.edu (P.W.J.); haussler@email.arizona.edu (M.R.H.); gkw@email.arizona.edu (G.K.W.) Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA; irady@dermatology.wisc.edu (I.R.); roxanechamcheu@gmail.com (R.-C.N.C.) Department of Zoology, Faculty of Science, Al-Azhar University, P.O. Box 11884 Nazr City, Cairo, Egypt School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ 85306, USA; msabir@asu.edu (M.S.S.); smallic5@asu.edu (S.M.) Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health & Pharmaceutical Sciences, University of Louisiana at Monroe, 1800 Bienville Drive, Bienville 362, Monroe, LA 71201, USA Correspondence: chamcheu@ulm.edu; Tel.: +1-318-342-6820 These authors contributed equally to this work. Funding Information: This work was supported in part by grants NIH DK033351 to M.R.H., NIH CA140285 to P.W.J., a POHOFI Inc., Pre-College Intern Scholarship Award to R.C.N.C., a American Skin Association (ASA) Carson Research Scholar Award in Psoriasis to J.C.C., a UW-Madison Skin Disease Research Center (SDRC) Pilot and Feasibility Research Award to J.C.C. from NIH/NIAMS grant P30 AR066524, funding from the University of Louisiana at Monroe School of Pharmacy to J.C.C., and a grant from the University of Arizona, Department of Basic Medical Sciences to G.K.W. Funding Information: Acknowledgments: This work was supported in part by grants NIH DK033351 to M.R.H., NIH CA140285 to P.W.J., a POHOFI Inc., Pre-College Intern Scholarship Award to R.C.N.C., a American Skin Association (ASA) Carson Research Scholar Award in Psoriasis to J.C.C., a UW-Madison Skin Disease Research Center (SDRC) Pilot and Feasibility Research Award to J.C.C. from NIH/NIAMS grant P30 AR066524, funding from the University of Louisiana at Monroe School of Pharmacy to J.C.C., and a grant from the University of Arizona, Department of Basic Medical Sciences to G.K.W. Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2018",
month = feb,
day = "4",
doi = "10.3390/nu10020174",
language = "English (US)",
volume = "10",
journal = "Nutrients",
issn = "2072-6643",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",
}