Polyinosinic:polycytidylic acid aggravates calcipotriol-induced atopic dermatitis-like skin lesions in mice by increasing the expression of thymic stromal lymphopoietin.

BACKGROUND

Polyinosinic:polycytidylic acid [poly (I:C)] is a synthetic viral double-stranded RNA analog that can activate Toll-like receptor 3 (TLR3) and induce the release of thymic stromal lymphopoietin (TSLP). TSLP has been shown to contribute to atopic dermatitis (AD). This study explored the effects of poly (I:C) in a calcipotriol-induced model of murine AD.

METHODS

Calcipotriol (MC903) was used to establish AD-like mice model. Mice in the MC903 + poly (I:C) group were then treated with poly (I:C) in a concentration of 5 µg/g bodyweight. The impact of poly (I:C) treatment on these animals was assessed based upon changes in lesions, bodyweight, ear thickness, and histopathological findings. In addition, serum interleukin 4 (IL-4), interferon-γ (IFN-γ), immunoglobulin E (IgE), IL-13, and TSLP levels were measured using enzyme-linked immunosorbent assay (ELISA), while tissue IL-13 and TSLP levels were assessed using ELISA, Western blotting, and immunohistochemical staining, and mast cell infiltration was assessed through toluidine blue (TBO) staining.

RESULTS

Relative to vehicle control treatment, poly (I:C) administration was associated with a significant exacerbation of calcipotriol-induced AD-like murine skin lesions. In animals treated with poly (I:C), the levels of serum IL-4, IL-13 and TSLP increased significantly, while the level of IFN-γ did not change. It also increased IL-13 and TSLP levels in skin lesions relative to the control-group mice and increased dermal mast cell infiltration and IgE production.

CONCLUSIONS

These data indicate that poly (I:C) treatment and exogenous activation of TLR3 exacerbate murine calcipotriol-induced AD-like skin lesions in part by increasing the production of TSLP and other T-helper 2 (Th2)-related cytokines.

KEYWORDS

Atopic dermatitis (AD); polyinosinic:polycytidylic acid [poly (I:C)]; thymic stromal lymphopoietin (TSLP); Toll-like receptor 3 (TLR3).