Polyphenols and Cannabidiol Modulate Transcriptional Regulation of Th1/Th2 Inflammatory Genes Related to Canine Atopic Dermatitis

Abstract

Canine atopic dermatitis (AD) is a multifactorial allergic disease associated with immune and abnormal skin barrier dysfunction and it is one of the primary causes of pruritus. Using a novel <i>in vitro</i> model of AD, here we tried to revert the alteration of transcriptional regulation of AD canine key genes testing a nutraceutical mixture containing flavonoids, stilbene, and cannabinoids, which are already well-known for their applications within dermatology diseases. The nutraceutical mixture induced in inflamed cells a significant downregulation (<i>p</i> < 0.05) of the gene expression of <i>ccl2, ccl17</i>, and <i>tslp</i> in keratinocytes and of <i>ccl2, ccl17</i>, and <i>il31ra</i> in monocytes. Consistent with the observed alterations of <i>tslp, ccl2, ccl17</i>, and <i>il31ra</i> messenger RNA (mRNA) levels, a significant increase (<i>p</i> < 0.05) of DNA methylation at specific CpG sites on the gene regulatory regions was found. These results lay the foundation for the use of these natural bioactives in veterinary medicine and provide a model for deeper understanding of their mechanisms of action, with potential translation to human research.