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 in vitro 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 (p < 0.05) of the gene expression of ccl2, ccl17, and tslp in keratinocytes and of ccl2, ccl17, and il31ra in monocytes. Consistent with the observed alterations of tslp, ccl2, ccl17, and il31ra messenger RNA (mRNA) levels, a significant increase (p < 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.
Highlights
In veterinary dermatology practice, canine atopic dermatitis (AD) is a multifactorial allergic disease that affects up to 27% of dogs; it is associated with immune and abnormal skin barrier dysfunction and it is one of the primary causes of pruritus [1]
Canine monocyte-macrophage, DH82 (ATCC, Manassas, VA, USA) and canine epidermal keratinocyte progenitor (CPEK; CELLnTEC, Bern, Switzerland) cell lines were grown at 37◦C in humidified 5% CO2 atmosphere, in accordance with the manufacturer’s recommended protocols
The effects evoked by the inflammatory stimulation on canine DH82 and CPEK cells on the expression of selected genes were assessed by real-time PCR, and the results are shown in Table 3 (CPEK cell line; “keratinocytes”) and 4 (DH82 cell line; “monocytes”)
Summary
Canine atopic dermatitis (AD) is a multifactorial allergic disease that affects up to 27% of dogs; it is associated with immune and abnormal skin barrier dysfunction and it is one of the primary causes of pruritus [1]. Due to their low toxicity and high efficacy, nutraceuticals are helpful for AD prevention and treatment [3]. Nutrigenomic studies in humans and animal models have clearly shown that nutraceuticals can influence signaling processes, cell apoptosis, metabolism, immune regulation, and modulate gene expression through epigenetic control [4, 5]. Atopic dermatitis treatment represents a challenge in human medicine, given the high incidence and the substantial psychosocial burden involved; for these reasons, many studies are focused on characterizing the disease pathomechanisms in our and other species to find an optimal Taking into account epigenetic modulations within AD and considering the importance of environment in disease progression, food supplements can delay the onset and improve the prognosis of the disease, giving support when anti-inflammatory feedback mechanisms fail to switch off, thereby avoiding an inflammatory over-response [6].
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