Format

Send to

Choose Destination
Sci Rep. 2017 Sep 11;7(1):11198. doi: 10.1038/s41598-017-10580-y.

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

Author information

1
Department of Dermatology, Emory University School of Medicine, Atlanta, GA, 30322, USA. jarbise@emory.edu.
2
Veterans Affairs Medical Center, Decatur, GA, 30322, USA. jarbise@emory.edu.
3
Case Western Reserve University, Cleveland, OH, 44106, USA.
4
Department of Dermatology and Allergology Technische Universität München, München, Germany.
5
Department of Dermatology, University of Alabama, Birmingham, AL, 35294, USA.
6
Department of Dermatology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
7
Veterans Affairs Medical Center, Decatur, GA, 30322, USA.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center