Abstract
Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes and a pro-inflammatory milieu in the skin. While patients with moderate to severe psoriasis are treated using targeted therapies (small molecules and monoclonal antibodies), patients suffering from milder forms are still in need of effective topical products without adverse effects. Antimony compounds (ACs) are regularly used as anti-inflammatory compounds in traditional and anthroposophic medicine and as antiprotozoan drugs. Here, we examined the effect of metallic antimony, natural antimony(III) sulfide and potassium antimonyl(III) tartrate in vitro on psoriasis-like keratinocytes and the human dendritic cell line THP-1 using qPCR, immunocytochemistry, ELISA and flow cytometry. In psoriatic keratinocytes, ACs inhibited the overexpression of the antimicrobial peptide β-defensin 2 and glucose transporter 1, as well as the hyperproliferation marker keratin 17. Furthermore, ACs mediated anti-inflammatory effects by reducing nuclear translocation of the p65 subunit of NF-κB and pSTAT3 and inhibited pro-inflammatory cytokine secretion by keratinocytes. In addition, ACs displayed anti-psoriatic effects by reducing the activation of IFN-α-treated THP-1 cells as well as the expression of the psoriasis-promoting master cytokine IL-23 by these cells. While all ACs showed anti-psoriatic effects, the most prominent results were seen with potassium antimonyl(III) tartrate. In summary, ACs display numerous anti-psoriatic effects in vitro at subtoxic concentrations. We conclude that ACs are interesting compounds for the topical treatment of psoriasis that warrant further investigation in clinical studies.
Highlights
Psoriasis is a chronic inflammatory skin disease with an estimated global prevalence of 2–3% [1]
While IL-22 is responsible for the characteristic epidermal hyperplasia and reduced differentiation of keratinocytes accompanied by parakeratosis, IL-17A activates important signaling pathways including the Janus kinase/signal transducer and activator of transcription-(JAK/STAT) as well as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in keratinocytes
This results in the secretion of several pro-inflammatory mediators (e.g., IL-6 or IL-8) and the expression of typical psoriasis markers such as keratin 17 (KRT17) or glucose transporter 1 (GLUT1) by the keratinocytes
Summary
Psoriasis is a chronic inflammatory skin disease with an estimated global prevalence of 2–3% [1]. While IL-22 is responsible for the characteristic epidermal hyperplasia and reduced differentiation of keratinocytes accompanied by parakeratosis, IL-17A activates important signaling pathways including the Janus kinase/signal transducer and activator of transcription-(JAK/STAT) as well as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in keratinocytes This results in the secretion of several pro-inflammatory mediators (e.g., IL-6 or IL-8) and the expression of typical psoriasis markers such as keratin 17 (KRT17) or glucose transporter 1 (GLUT1) by the keratinocytes. The uncovering of these pathways led to the development of targeted therapies, i.e., monoclonal antibodies against TNF-α, IL-12/23, IL-23 and IL-17A [8,9,10]. DEFB4A and KRT17 showed the most beneficial changes upon treatment with either A or PAT
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