Chitin nanofibrils suppress skin inflammation in atopic dermatitis-like skin lesions in NC/Nga mice
Introduction
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is increasingly prevalent and has reached epidemic proportions in children worldwide (Odhiambo et al., 2009, Williams et al., 2008). Topical corticosteroids are the first-line therapy for the treatment of AD (Eichenfield et al., 2014). Systemic administration of glucocorticoids is effective against AD (Sidbury & Hanifin, 2000), but there are many side effects, including cushingoid features, cataracts, hyperglycemia, moon facies, body weight loss, hypokalemia, and osteopenia (Harada et al., 2009, Sidbury and Hanifin, 2000).
Previously, the immunologic effects of chitin have been explored (Bae, Shin, Kim, Kim, & Shon, 2013; Da Silva et al., 2009; Nishimura et al., 1984; Shibata, Foster, Bradfield, & Myrvik, 2000). For example, exogenous chitin activates adaptive type-2 allergic inflammation (Shibata et al., 2000). Da Silva et al. (2009) described the size-dependent regulation of innate immunity by chitin. It is described only small chitin (SC; <40 μm, largely 2–10 μm) induced IL-10 elaboration. The effects of intermediate-sized chitin (40–70 μm) were mediated by pathways that involve toll like receptor (TLR) 2, dectin-1, and nuclear factor κB (NF-κB). In contrast, the effects of SC were mediated by TLR2-dependent and -independent, as well as dectin-1-dependent pathways that involved the mannose receptor and spleen tyrosine kinase.
Recently, several methods of preparing chitin nanofibrils have been reported (Azuma, Isuku, Osaki, Okamoto, & Minami, 2014; Ifuku, 2014; Ifuku & Saimoto, 2012). Ifuku et al. (2009) prepared chitin nanofibrils (CNFs) via a simple grinding treatment under an acidic condition. The beneficial effects of CNFs to the skin have previously been reported (Morganti, Muzzarelli, & Muzzarelli, 2006; Morganti & Morganti, 2008). Their enormous surface allows CNFs to interact with enzymes, platelets, and other cell compounds present in living tissues. Thus, the peculiarity and ability for granulation tissue is accompanied by angiogenesis and regular deposition of collagen fibers with the consequent enhanced and correct repair of dermoepidermal lesions (Morganti and Morganti, 2008, Morganti et al., 2006). Recently, Ito et al. (2014) reported beneficial effects of CNFs to the skin in an experimental skin model. The application of CNFs to skin improved the epithelial granular layer and increased granular density. Furthermore, CNF application to the skin resulted in a lower production of TGF-β compared to that in the control group. Izumi et al. (2015) reported that surface-modified CNFs promote wound healing. In this study, it is showed that CNFs, before surface modification, induce only a slight inflammation in the skin. This evidence indicates that CNFs have a high biocompatibility to the skin.
To the best of our knowledge, the effects of CNFs on skin inflammations like AD has never been evaluated. Herein, we applied CNFs in an experimental AD-like skin lesion model. We evaluated the effects of CNFs on a developmental or early-stage model of AD. Furthermore, its effects were compared to that of corticosteroid treatment.
Section snippets
Animals
NC/Nga mice (5-week-old, females) were purchased from SLC, Inc. (Shizuoka, Japan). Mice were kept under conventional conditions. The animals were reared in a room with the temperature controlled at 22 ± 2 °C, humidity at 50 ± 5%, and lighting set at 12:12-h light/dark cycles (light cycle, 7:00–19:00 h). All mice had a normal diet, with free access to food (CE-2, Japan CLEA, Osaka, Japan) and tap water during the experimental periods. The animal procedures in this study were approved by the Animal
Clinical and histological changes upon application of CNFs in development of AD-like skin lesion
The body weight changes during the experimental period are shown in Fig. 2A. No change in body weight was observed during the experimental period. Gross changes in the appearance of the skin are shown in Fig. 2B. The clinical scoring of dermatitis severity is presented in Fig. 3. In the NT group, the dermatitis score increased over time during the experimental period. In the CNFs group, the dermatitis score also increased, however, the scores were lower than those of the control and chitin
Acknowledgements
This work was financially supported by the Creating STart-ups from Advanced Research and Technology (START) project of JST and by KAKENHI (26708026) of JSPS.
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These authors contributed equally to this work.