마우스에 유도된 알러지성 피부염증에 대한 어유의 효과

Abstract

Allergic skin inflammation such as atopic dermatitis (AD) is characterized by pruritus and inflammation. Histamine and various cytokines are the main pruritogens causing edema and itching. Increased levels of serum immunoglobulin E (IgE) and infiltration of inflammatory cells in skin lesions also mark allergic skin inflammation. Thymic stromal lymphopoietin (TSLP), in particular, strongly activates the maturation of dendritic cells within the epidermis, and can regulate the allergic inflammation reaction. Regulatory T cells (Tregs) play a key role in various immune responses and prevent or suppress the differentiation, proliferation and function of various immune cells, including cluster of differentiation 4 (CD4) + T cells. Moreover, since all Tregs express CD25 at the cell surface and have forkhead box P3 (Foxp3) as a transcription factor, CD25 and Foxp3 have been identified as makers of Tregs. Fish oil (FO) contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) called omega-3 fatty acids polyunsaturated fatty acids (n-3 PUFAs). The n-3 PUFAs in fish oil have been studied in a variety of diseases and are known to reduce inflammation responses in allergic patients. Recently, some studies have explored the effects of fermentation on the characteristics of various foods such as wine, yogurt and cheese. Fermentation has tremendous abilities to transform the chemical structure of constituents or to create new substances. In the present study, we investigated the effects of the fermentation of fish oil using fermented fish oil (FFO) and natural fish oil (NFO) on the modulation of the immune system. Results reveal that, FFO alleviates various immune disorder symptoms and up-regulates CD4+CD25+Foxp3+ regulatory T cells (Tregs). In comparison with the induction group, the administration of FFO or NFO decreased scratching behavior, cutaneous edema, inflammatory cell infiltration, expression of TSLP, serum IgE and histamine levels. Both FFO and NFO treatment regulated the expression of AD-associated pro-/anti-inflammatory cytokines (IL-4, -13, IFN-ɣ and TGF-ϐ) and transcription factors (Foxp3, T-bet and GATA3) at the sites of inflammation. However, FFO-treated group showed stronger inhibitory effects on various experimental AD symptoms than NFO-treated group. Although FFO or NFO treatment did not increase the Foxp3 level and there was no difference in the CD4+CD25+ Treg population compared with the normal group, the FFO treatment increased expression of Treg-associated factors (TGF-? and IL-10), resulting in significantly elevated suppressor activity compared with NFO-treated group. In addition, ingestion of FFO increased Foxp3 level and CD4+CD25+Foxp3+ Treg population in anti-CD3&28-stimulated CD4+ T cells compared with NFO. These results suggest that the anti-allergic effect of FFO is associated with enrichment of CD4+CD25+Foxp3+ Treg at the inflamed sites and FFO may be effective source for improving the allergic symptoms of AD.