1. Introduction
Atopic dermatitis (AD) is a chronic inflammatory skin disease with typical symptoms like severe itching and recurrent eczema-like lesions [1], which affects 5% to 20% of children and 2% to 10% of adults worldwide [2, 3]. The pathophysiology of AD may involve a complex interaction between genetic and environmental factors that are associated with immunity, skin barrier dysfunction, pruritus and other factors [4]. Although there is no cure for AD, treatment can decrease dryness and irritation. Steroids or calcineurin inhibitors are the most commonly used medication. Yet, those drugs may not always be effective and may induce side effects, especially if used in children over a longer time [5]. Thus, there is an urgent need to further explore the exact mechanism of pathogenesis in order to find effective therapeutic targets for the treatment of AD.
TRPA1 is a six-time transmembrane protein that belongs to the TRP channel family, which is activated under some environmental stimuli, such as low temperature, acidic environment and hydrogen peroxide rich environment [6, 7]. TRPA1 is expressed in peripheral sensory nerve fibers, but also a variety of cells, such as cutaneous keratinocytes, mast cells, endothelial and dendritic cells. It is also involved in inflammation, neuropathic pain and is a key downstream signal of histamine-independent pruritus [8, 9]. Recent evidence suggests that TRPA1 has a vital role in pruritus. Studies have shown that hapten oxazolidone (Oxa) and squaric acid dibutylester (SADBE) can directly activate the TRPA1 channel and participate in inducing itching in allergic contact dermatitis. For example, Oxa-induced skin inflammation has been alleviated in TRPA1 deficiency mice while SADBE-induced skin inflammation remains [10, 11]. Moreover, Imiquimod (IMQ) can directly activate the TRPA1 channel and has an inflammatory protective role in psoriasiform dermatitis [12, 13]. Recent studies have found that TRPA1 is highly expressed in skin lesions of AD patients with severe pruritus [14]. Although the role of TRPA1 in AD pruritus has been widely reported, the effect of TRPA1 in the pathogenesis of AD, especially in the regulation of inflammation of AD and the therapeutic effect of anti-TRPA1 in the treatment of AD, remains unknown.
DNCB, a hapten that can activate the TRPA1 channel of HEK cells [15,16], can be used to further explore the role of TRPA1 in the pathogenesis of AD. The aim of this study was to investigate the role of TRPA1 in the pathogenesis of DNCB-induced AD in mice.
Materials and methods
2.1 Animals
TRPA1-/- mice were purchased from the Jackson Laboratories (Bar Harbor, ME, USA), while the C57/BL6 mice were purchased from the Animal Centre of Chongqing Medical University (Chongqing, China). All the animals were housed in an environment with a temperature of 22 ± 1 ºC, relative humidity of 50 ± 1%, and a light/dark cycle of 12/12 hr. All animal studies (including the mice euthanasia procedure) were done in compliance with the regulations and guidelines of Chongqing medical University institutional animal care and were conducted according to the AAALAC and the IACUC guidelines. All mice in all the experiments were 12-weeks old (20-25g).