Abstract
To illuminate the anti-allergy mechanism of astragaloside IV (AS-IV), we assessed its effects in a murine model of allergic contact dermatitis (ACD). AS-IV administered in the sensitization phase, rather than in the elicitation phase, dramatically alleviated the symptoms of allergic inflammation. We hypothesized that AS-IV exerts its anti-allergy effects by regulating the production of key pro-allergic cytokines based on the fact that interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) levels increase significantly in the initial stage of the sensitization phase. AS-IV administered in the initial stage of ACD inhibited TSLP and IL-33 expression and reduced the proportion of type-2 innate lymphoid cells (ILC2s). An in vitro study showed that the production of pro-allergic cytokines was significantly inhibited in AS-IV presenting HaCaT cells. We also verified that AS-IV administered only in the initial stage markedly alleviated inflammation, including ear swelling, Th2 cytokine expression, and histological changes. Taken together, these results suggest that AS-IV effectively ameliorates the progression of allergic inflammation by inhibiting key initiating factors, including TSLP and IL-33, and can be used to prevent and/or treat patients with ACD. Our data also suggest that these key pro-allergic cytokines are potential therapeutic targets for allergic diseases.
Highlights
Which produce large amounts of type-2 cytokines, such as IL-5 and IL-13, in allergic disorders[13]
Based on the use of A. membranaceus to treat the recurrence of several allergic diseases, we investigated the effects of AS-IV, the major active component of A. membranaceus, on a model of Th2 allergic contact dermatitis (ACD)
Our results show that AS-IV inhibits the inflammation of ACD and markedly alleviates this inflammation when administered in the sensitization phase rather than in the elicitation phase, indicating that AS-IV exerts specific effects in the sensitization phase
Summary
Which produce large amounts of type-2 cytokines, such as IL-5 and IL-13, in allergic disorders[13]. Thymic stromal lymphopoietin (TSLP) is another crucial epithelium-derived cytokine. It exerts its biological functions by binding to the TSLP receptor (TSLPR) and activates dendritic cells (DCs) to induce naïve CD4+ T cells to differentiate into inflammatory Th2 cells by upregulating the expression of the tumor necrosis factor (TNF) superfamily protein OX40L18–20. TSLP acts as a potent stimulator of Th2 cytokines and induces the proliferation, differentiation, and activation of mast cells[25]. Fluorescein isothiocyanate (FITC)-induced ACD, which is a Th2-dominant disease[26], was selected as a typical model of allergic disease. In contrast to 2,4-dinitrochlorobenzene (DNCB)-induced Th1-dominant ACD, the FITC-induced ACD model appropriately reproduces the key features of allergic inflammation. We tested the effects of AS-IV after different periods of exposure on various phases of the FITC-induced ACD model and investigated the underlying mechanisms
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