Anti-Inflammatory and Pro-Differentiating Properties of the Aryl Hydrocarbon Receptor Ligands NPD-0614-13 and NPD-0614-24: Potential Therapeutic Benefits in Psoriasis.
Giorgia CardinaliEnrica FloriArianna MastrofrancescoSarah MoscaMonica OttavianiMaria Lucia Dell'AnnaMauro TruglioAntonella VentoMarco ZaccariniChristos C ZouboulisMauro PicardoPublished in: International journal of molecular sciences (2021)
The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor expressed in all skin cell types, plays a key role in physiological and pathological processes. Several studies have shown that this receptor is involved in the prevention of inflammatory skin diseases, e.g., psoriasis, atopic dermatitis, representing a potential therapeutic target. We tested the safety profile and the biological activity of NPD-0614-13 and NPD-0614-24, two new synthetic AhR ligands structurally related to the natural agonist FICZ, known to be effective in psoriasis. NPD-0614-13 and NPD-0614-24 did not alter per se the physiological functions of the different skin cell populations involved in the pathogenesis of inflammatory skin diseases. In human primary keratinocytes stimulated with tumor necrosis factor-α or lipopolysaccharide the compounds were able to counteract the altered proliferation and to dampen inflammatory signaling by reducing the activation of p38MAPK, c-Jun, NF-kBp65, and the release of cytokines. Furthermore, the molecules were tested for their beneficial effects in human epidermal and full-thickness reconstituted skin models of psoriasis. NPD-0614-13 and NPD-0614-24 recovered the psoriasis skin phenotype exerting pro-differentiating activity and reducing the expression of pro-inflammatory cytokines and antimicrobial peptides. These data provide a rationale for considering NPD-0614-13 and NPD-0614-24 in the management of psoriasis.
Keyphrases
- atopic dermatitis
- wound healing
- soft tissue
- anti inflammatory
- endothelial cells
- oxidative stress
- transcription factor
- signaling pathway
- rheumatoid arthritis
- stem cells
- induced pluripotent stem cells
- poor prognosis
- lps induced
- machine learning
- cell therapy
- risk assessment
- binding protein
- toll like receptor
- big data
- data analysis