Salubrinal Ameliorates DNCB-Induced Atopic Dermatitis by Suppressing the NF-κB/NLRP3 Axis

Abstract

Background: Atopic dermatitis (AD) is an inflammatory skin disease with a considerable prevalence globally. The anti-inflammatory ability of salubrinal has been expounded in various disease models. However, the effect of salubrinal on AD was unknown. Methods: The AD model was constructed in mice via the administration of 1-chloro-2,4-dinitrochlorobenzene (DNCB). The effect of salubrinal on the symptoms and pathology of AD mice was assessed by clinical skin score, hematoxylin-eosin (HE) and toluidine blue (TB) staining and enzyme-linked immunosorbent assay (ELISA). The role of salubrinal in inflammation, endoplasmic reticulum (ER) stress and oxidative stress were investigated by ELISA, colorimetric detections and western blotting. Additionally, the potential mechanisms were explored by western blot. Results: Salubrinal ameliorated AD-like symptoms, such as increased skin thickness, erythema, scarring and dryness, and dermatitis scores in DNCB-stimulated mice. Salubrinal also improved DNCB-induced pathology in AD mice, as evidenced by the remittance of pathological manifestations, and the reduction of the infiltration of mast cells and the serum concentration of histamine. Moreover, salubrinal counteracted the DNCB-induced production of inflammatory factors, reactive oxygen species (ROS) and malondialdehyde (MDA) and the enhanced expression of proteins involved in the endoplasmic reticulum (ER) stress, but restored the expression of glutathione peroxidase (GSH-Px) and catalase (CAT) in AD mice. Mechanically, salubrinal decreased the relative protein levels of p-p65/p-65, and the relative expression of proteins involved in the NOD (nucleotide-binding domain)-like receptor protein 3 (NLRP3) inflammasome. Conclusions: Salubrinal ameliorated DNCB-induced atopic dermatitis through suppressing inflammation, ER stress and oxidative stress via attenuation of the nuclear factor-kappa B (NF-κB)/NLRP3 axis.