Abstract
Atopic dermatitis (AD) is a common inflammatory skin disease predominately related to Type 2 helper T (Th2) immune responses. In this study, we investigated whether piperine is able to improve AD symptoms using a trimellitic anhydride (TMA)-induced AD-like mouse model. Topical treatment with piperine reduced ear swelling (ear thickness and epidermal thickness) induced by TMA exposure. Furthermore, piperine inhibited pro-inflammatory cytokines such as TNF-α and IL-1β in mouse ears, compared with the TMA-induced AD group. In measuring allergic immune responses in draining lymph nodes (dLNs), we found that IL-4 secretion, GATA3 mRNA level, and STAT6 phosphorylation were suppressed by piperine treatment. In an ex vivo study, piperine also inhibited the phosphorylation of STAT6 on the CD4+ T cells isolated from splenocytes of BALB/c mice, and piperine suppressed IL-4-induced CCL26 mRNA expression and STAT6 phosphorylation in human keratinocytes resulting in the inhibition of infiltration of CCR3+ cells into inflammatory lesions. These results demonstrate that piperine could ameliorate AD symptoms through suppression of Th2-mediated immune responses, including the STAT6/GATA3/IL-4 signaling pathway. Therefore, we suggest that piperine is an excellent candidate as an inhibitor of STAT6 and may help to improve AD symptoms.
Highlights
Atopic dermatitis (AD) is a common inflammatory skin disease that has increased in prevalence over the past decades
Since trimellitic anhydride (TMA) treatment can induce allergic dermatitis via Th2-dominant immune responses, we used a TMA-induced AD-like mouse model, induced by the method following the schedule in Figure 1, and investigated the effects of direct topical treatment of the ears with piperine (TMA-exposed lesion)
These,When the Th2-mediated immune response is a major reaction with regard to IL-4 production, which ears were stimulated by TMA, the draining lymph nodes (dLNs) of a mouse play an integral role in peripheral we investigate further.to investigate the effects of piperine on Th2-associated immune immune responses
Summary
Atopic dermatitis (AD) is a common inflammatory skin disease that has increased in prevalence over the past decades. The fundamental cause of AD is not completely understood, but its pathogenesis has been associated with immune dysfunction. AD patients predominantly show Type 2 helper T2(Th2) inflammatory responses. Eighty-five percent of AD occur before the age of 5 years, and pediatric patients show a Th1/Th2 imbalance with a predominant Th2 immune response [1,2]. Naïve CD4+ T helper cells differentiate into functionally distinct subsets of effector T helper cells by recognizing the antigen presented by the “antigen-presenting cells” (APC) via the T cell receptor complex [3,4]. Among the subsets of effector T cells, Th1 cells are developed upon exposure to interleukin (IL)-12 and secrete interferon (IFN)-γ. Th2 cells produce Th2 cytokines, such as IL-4, Molecules 2020, 25, 2186; doi:10.3390/molecules25092186 www.mdpi.com/journal/molecules
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