Tacrolimus Inhibits TNF- α/IL-17A-Produced pro-Inflammatory Effect on Human Keratinocytes by Regulating IκBζ

This study aimed to investigate the potential regulatory effect of tacrolimus on TNF- α/ IL-17A-costimulated human keratinocytes in the mimic psoriatic microenvironment. The cultured normal human keratinocytes (NHKs) were divided into the following groups: control, TNF-α/IL-17A, tacrolimus, and TNF-α/IL-17A + tacrolimus. Cultured cells and supernatant were collected after 24  h, and then real-time quantitative PCR, western blot, and ELISA analysis were performed. Foreskin tissues were treated by using TNF-α, IL-17A, and tacrolimus 0.03% ointment and then cultured for 24 h, and immunohistochemistry was performed. NHKs expressed significant IL-36γ, CCL-20, IL-1β, S100- A9, and CXCL-1 mRNA after TNF-α/IL-17A treatment. Tacrolimus significantly inhibited TNF-α/IL-17A-induced IL-36γ, CCL-20, IL-1β, and S100-A9 expression at gene level and IL-36γ and CCL-20 expression at protein level. We further discovered TNF-α/IL-17A induced significant IκBζ mRNA and protei n expression in NHKs, which could be inhibited by tacrolimus. Tacrolimus can inhibit pro-inflammatory synergistic action of TNF-α/IL-17A on human keratinocytes by regulating IκBζ expression.
Source: Inflammation - Category: Allergy & Immunology Source Type: research