The natural compound PEITC ameliorates imiquimod-induced psoriasis in mice by suppressing neutrophil extracellular traps formation

Neutrophil extracellular traps (NETs) play a key role in the development of psoriasis, a chronic inflammatory skin condition. We demonstrate the effects and possible mechanisms of phenethyl isothiocyanate (PEITC) in inhibiting NETs and alleviating psoriasis. In response to imiquimod (IMQ), multiple symptoms including scaly plaques and associated skin inflammations were induced in mice. IMQ additionally promotes the formation of NETs and the levels of inflammatory factors. Interestingly, a natural compound PEITC exerted an intensive activity in the treatment of psoriasis. It improved lesions and ameliorated ischemic coagulation symptoms in the dorsal skin of mice. PEITC also significantly reduced the expression of inflammatory factors in mice skin with an inhibition on NETs-related molecules, such as myeloperoxidase, neutrophil elastase and citrullinated histone H3. 16S rRNA sequencing analysis demonstrated that IMQ treatment induced significant gut microbiota dysbiosis in mice, suggesting potential detrimental effects on intestinal microbial homeostasis. However, PEITC administration did not show a statistically significant ameliorative effect on this IMQ-induced microbial imbalance. In vitro experiments demonstrated that PEITC significantly suppressed lipopolysaccharide (LPS)-induced NET formation, suggesting that its therapeutic effects in psoriasis may be due to the inhibition of bacterially driven neutrophil activation. Therefore, we identified PAD4, an important enzyme for post-translational modification of proteins in the production of NETs, as a new potential target of PEITC. Taken together, our findings suggest that PEITC could be a novel potential therapeutic drug to relieve psoriasis via the inhibition of NETs both in vitro and in vivo.