About this item:

168 Views | 242 Downloads

Author Notes:

Correspondence and requests for materials should be addressed to J.L.A. (email: jarbise@emory.edu)

See publication for full list of author contributions.

The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

Emory and Mercer University have applied for patents for solenopsin derivatives.

Subject:

Research Funding:

This study was supported in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities.

Additional support was provided by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454.

Dr. Arbiser is supported by NIH RO1 AR47901.

Dr. Ward is supported by The Lozick Discovery Grant, National Psoriasis Foundation, the Murdough Family Center of Psoriasis, the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (P30 AR39750, P50 AR055508, R01 AR063437, R01 AR062546; R21 AR063852, R01 AR069071).

Evidence for biochemical barrier restoration: Topical solenopsin analogs improve inflammation and acanthosis in the KC-Tie2 mouse model of psoriasis.

Show all authors Show less authors

Tools:

Journal Title:

Scientific Reports

Volume:

Volume 7, Number 1

Publisher:

, Pages 11198-11198

Type of Work:

Article | Final Publisher PDF

Abstract:

Psoriasis is a chronic inflammatory skin disease affecting 2.5-6 million patients in the United States. The cause of psoriasis remains unknown. Previous human and animal studies suggest that patients with a susceptible genetic background and some stimulus, such as barrier disruption, leads to a coordinated signaling events involving cytokines between keratinocytes, endothelial cells, T cells, macrophages and dendritic cells. Ceramides are endogenous skin lipids essential for maintaining skin barrier function and loss of ceramides may underlie inflammatory and premalignant skin. Ceramides act as a double-edged sword, promoting normal skin homeostasis in the native state, but can be metabolized to sphingosine-1-phosphate (S1P), linked to inflammation and tumorigenesis. To overcome this difficulty, we synthesized solenopsin analogs which biochemically act as ceramides, but cannot be metabolized to S1P. We assess their in vivo bioactivity in a well-established mouse model of psoriasis, the KC-Tie2 mouse. Topical solenopsin derivatives normalized cutaneous hyperplasia in this model, decreased T cell infiltration, interleukin (IL)-22 transcription, and reversed the upregulation of calprotectin and Toll-like receptor (TLR) 4 in inflamed skin. Finally, they stimulated interleukin (IL)-12 production in skin dendritic cells. Thus suggesting barrier restoration has both a biochemical and physical component, and both are necessary for optimal barrier restoration.

Copyright information:

© The Author(s) 2017

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote