How products like Dovonex works for psoriasis

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This study looked at the working of antipsoriatic effect of calcipotriol.

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Background:
Calcipotriol ameliorates psoriasis through inducing keratinocyte apoptosis and inhibiting nuclear factor kappa B (NF-κB) activation, while zinc finger protein A20 exhibits an anti-apoptotic effect on various types of cells.

Objectives:
To understand the potential role of A20 in calcipotriol function.

Materials and methods:
The A20 levels were evaluated in the psoriatic skins from both human patients and K14-vascular endothelial growth factor (VEGF) transgenic mice that received or did not receive topical calcipotriol treatment. The in vitro effect of calcipotriol on A20 expression and the downstream NF-κB pathway was studied using a model of human foreskin keratinocytes (HFKs) that were stimulated with psoriatic cytokines [M5, a cocktail of interleukin (IL)-1a, IL-17A, IL-22, Oncostatin M and tumour necrosis factor-α, each at 10 ng mL−1].

Results:
A20 expression was enhanced in both psoriatic tissues and keratinocytes when compared with controls, but decreased on calcipotriol treatment. The transfection of A20 small interfering RNA (siRNA) improved cell differentiation, and inhibited psoriatic inflammation in a HFK model. Moreover, the nuclear expression of NF-κB p65 decreased on A20 downregulation in psoriatic tissues and keratinocytes. Interestingly, calcipotriol enhanced the binding of A20 to ring finger protein 114 (RNF114) and A20-binding inhibitor of NF-κB-1 (ABIN-1) in HFKs, two negative regulators of the NF-κB pathway.

Conclusions:
Calcipotriol exhibits its antipsoriatic function through suppressing A20 expression and stabilizing negative regulators of the NF-κB pathway.

Source: onlinelibrary.wiley.com

Funding: This study was partially supported by the Youth Foundation of Natural Science Research Project of Jangsu Province and Psoriasis Vulgaris Foundation of Bright Future Pharmaceutical Laboratories Ltd, Chinese Society of Dermatology.