Abstract
Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways. Indeed, both polyols up-regulated the expression of filaggrin, loricrin, involucrin and occludin; yet, xylitol exerted somewhat more profound effects. Moreover, while both polyols stimulated the MAPK pathway, only xylitol induced the activation-dependent translocation of protein kinase Cδ, a key promoter of epidermal differentiation. Finally, in various keratinocyte inflammation models, both polyols (albeit with different efficacies) exerted anti-inflammatory effects. Taken together, these data strongly suggest that glycerol and xylitol differentially modulate expressions of multiple genes and activities of signalling pathways in epidermal keratinocytes. Thus, our findings invite clinical trials to explore the applicability and the impact of a combined glycerol-xylitol therapy in the management of various skin conditions.


![NA sensing by TLR7, TLR8 and TLR9. The liganded dimers of the extracellular domains of simian TLR7 [Protein Data Bank (PDB) ID: 5GMF], human TLR8 (PDB ID: 4R07) and horse TLR9 (PDB ID: 3WPC). TLR7 interacts with guanosine and the tri-ribonucleotide UUU. TLR8 binds to uridine and the di-nucleotide UG. TLR9 interacts with the ODN CpG. The figures were prepared with CueMol (http://www.cuemol.org). m_dxy01601.jpeg?Expires=1520598193&Signa](https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/intimm/30/2/10.1093_intimm_dxy016/1/m_dxy01601.jpeg?Expires=1520598193&Signature=YCF1xIAupSNrCRn-yMYVU3aWfbsWlXHY4Gp70ZqYKgMBapYkqAoB~BWF8ZW1LMw~j7Nq9Ms~N4Fd0MX~u~o64M-pAwNCA6faD0lrS7Vj4USLW~K-4Z9JjcEKeZ6QO6eP1WWXe1ja2B6VUc0RglgpoqaFGEPRVxz5~ipsaxR9~0RXud3mjjU5gk8RdG24h965KesCfbFVHMZQfLufvmA-FEKJEDeJvoP7w63CXPWpv10d6mmKGvzWR4jIh-mKGP~WlGXm-MzYYVj2kFsHY4jgtZ5SQ2BCOBS5zb9FijMskf2p3qQ-XidA5ZeFfeT2PfpFdPGjbjelQQVHteKLyk7kng__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q)
