15-deoxyprostaglandin-j2 and Dermatitis--Atopic

The present study examined the efficacy of the topical 15d‑PGJ2‑poloxamer 407 hydrogel in an atopic dermatitis (AD) animal model. The 15d‑PGJ2 hydrogel was prepared and characterized. The examined rats possessed AD‑Like cutaneous lesions, which were induced using 2,4‑dinitrochlorobenzene, the rats were then treated with a hydrogel vehicle, 15d‑PGJ2 hydrogel or tacrolimus for 14 days. The rats were sacrificed and blood samples were collected to quantify the IgE levels. Subsequently, skin biopsies were stained with toluidine blue to identify mast cells and immunohistochemistry was performed for ROR‑γt and TNF‑α. Histological analyses demonstrated that 15d‑PGJ2 hydrogel significantly decreased mast cell infiltration (P<0.05) when compared with the AD‑group. Tacrolimus at 0.1% exhibited decreased mast cell infiltration; however, this difference was not statistically significant from the AD‑group. Topical 15d‑PGJ2 hydrogel and Tacrolimus 0.1% significantly reduced the serum levels of IgE (P<0.05) compared with the AD‑group. Immunohistochemistry revealed a significant decrease in ROR‑γt and TNF‑α positive cell expression (P<0.05) in the 15d‑PGJ2 hydrogel group compared with the AD‑group. In summary, topical administration of 15d‑PGJ2 hydrogel had a beneficial effect on AD symptoms, suggesting that this formulation may be a useful strategy for the treatment of AD.

Topics: Administration, Topical; Animals; Dermatitis, Atopic; Dinitrochlorobenzene; Hydrogels; Immunoglobulin E; Immunohistochemistry; Immunosuppressive Agents; Male; Mast Cells; Nuclear Receptor Subfamily 1, Group F, Member 3; Prostaglandin D2; Rats; Rats, Wistar; Skin; Tacrolimus; Tumor Necrosis Factor-alpha

Thymic stromal lymphopoietin (TSLP) is produced by epidermal keratinocytes, and it induces Th2-mediated inflammation. TSLP expression is enhanced in lesions with atopic dermatitis, and is a therapeutic target. Antimycotic agents improve the symptoms of atopic dermatitis.. The objective of this study was to examine whether antimycotics suppress TSLP expression in human keratinocytes.. Normal human keratinocytes were incubated with polyinosinic-polycytidylic acid (poly I:C) plus IL-4 in the presence of antimycotics. TSLP expression was analyzed by ELISA and real time PCR. Luciferase assays were performed to analyze NF-κB activity. IκBα degradation was analyzed by Western blot analysis.. Poly I:C plus IL-4 increased the secretion and mRNA levels of TSLP, which was suppressed by an NF-κB inhibitor, and also enhanced NF-κB transcriptional activities and induced the degradation of IκBα in keratinocytes. The antimycotics itraconazole, ketoconazole, luliconazole, terbinafine, butenafine, and amorolfine suppressed the secretion and mRNA expression of TSLP, NF-κB activity, and IκBα degradation induced by poly I:C plus IL-4. These suppressive effects were similarly manifested by 15-deoxy-Δ-(12,14)-PGJ2 (15d-PGJ2), a prostaglandin D2 metabolite. Antimycotics increased the release of 15d-PGJ2 from keratinocytes and decreased the release of thromboxane B2, a thromboxane A2 metabolite. Antimycotic-induced suppression of TSLP production and NF-κB activity was counteracted by an inhibitor of lipocalin type-prostaglandin D synthase.. Antimycotics itraconazole, ketoconazole, luliconazole, terbinafine, butenafine, and amorolfine may suppress poly I:C plus IL-4-induced production of TSLP by inhibiting NF-κB via increasing 15d-PGJ2 production in keratinocytes. These antimycotics may block the overexpression of TSLP in lesions with atopic dermatitis.

Topics: Antifungal Agents; Cells, Cultured; Cytokines; Dermatitis, Atopic; Humans; Interleukin-4; Keratinocytes; NF-kappa B; Poly I-C; Prostaglandin D2; Recombinant Proteins; RNA, Messenger; Thymic Stromal Lymphopoietin