Abstract
Exposure to chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) has been associated with allergic contact dermatitis and occupational asthma. Despite this association however, no study has investigated the effects of CMIT/MIT exposure on the development of atopic dermatitis (AD). This study was conducted to investigate the influence of epicutaneous exposure to CMIT/MIT on AD in a mouse model and the underlying biological mechanisms. BALB/C mice were exposed to CMIT/MIT for 3 weeks and AD was developed using ovalbumin (OVA) epidermal sensitization. CMIT/MIT epicutaneous exposure in normal mice significantly enhanced AD-like phenotypes (e.g., transepidermal water loss, clinical score, total serum immunoglobulin E level and infiltration of inflammatory cells). In addition, CMIT/MIT exposure significantly augmented the mRNA expression level of T helper (Th) 2-related cytokines (thymic stromal lymphopoietin, interleukin (IL)-6 and IL-13), Th2 chemokine (chemokine (C-C motif) ligand 17) and the population of CD4+IL-4+ cells in the skin. Moreover, mice exposed to CMIT/MIT in the OVA challenge had greater AD-like phenotypes, higher IL-4 and IL-17A skin mRNA expression levels, and a larger population of CD4+IL-4+- and IL-17A+-producing cells in the skin-draining lymph nodes. Our current findings in a mouse model thus suggest that CMIT/MIT exposure may cause AD symptoms through the dysregulation of Th2/Th17-related immune responses.
Highlights
Atopic dermatitis (AD) is a chronic inflammatory skin disease which manifests as eczematous skin including epidermal hyperplasia, spongiosis and immune cell infiltration of the dermis[1,2]
The mice exposed to CMIT/MIT showed a higher level of inflammatory cell infiltration and greater epidermis thickness in the skin than the control mice exposed to PBS (Fig. 1c)
In assessments of the immune response in these mice, the animals exposed to CMIT/MIT had a higher expression of T helper (Th) 2-related cytokines/ chemokines (i.e. thymic stromal lymphopoietin (TSLP), interleukin (IL)-6, IL-13 and C-C motif chemokine (CCL)-17) in their skin (Fig. 2a–d), and greater populations of CD4+IL-4+ cells in the skin-draining lymph nodes (Fig. 2e,f) compared to the controls
Summary
Atopic dermatitis (AD) is a chronic inflammatory skin disease which manifests as eczematous skin including epidermal hyperplasia, spongiosis and immune cell infiltration of the dermis[1,2]. Epidemiological studies have provided evidence for a possible relationship between environmental pollution exposure, chemical substances, and the risk of AD5–8. A recent experimental study in mice has provided evidence www.nature.com/scientificreports of a biological basis for MIT as a risk factor for allergic sensitization, as indicated by enhanced skin inflammation, immunoglobulin E (IgE) production and immune responsiveness[18]. Despite the growing evidence for a relationship between CMIT/MIT exposure and an allergic immune response no previous studies have investigated an association between these chemicals and the development of AD. People who were exposed to HDs claim to have subsequently developed allergic diseases after using HDs. Recent evidence has shown that HD exposure increases the risk of asthma in children[24]. We investigated whether CMIT/MIT exposure affects AD development and immune responses in an AD mouse model
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