diisononyl-phthalate and Dermatitis--Allergic-Contact

The possible pathogenic role and mechanism of Di-iso-nonyl phthalate (DINP) in allergic dermatitis is still controversial. This work has shown that oral exposure to DINP exacerbated allergic dermatitis tissue lesions in FITC-sensitized mice. The lesions was accompanied by an enhancement of TRPA1 expression and an increase in IgG1, IL-6 and IL-13 levels. This work also found that blocking TRPA1 by HC030031 effectively prevented the development of allergic dermatitis resulting from oral exposure to DINP and/or FITC-sensitized mice. This result is marked by the down regulation of IgG1 levels, a reduction in mast cell degranulation and a decrease in IL-6 and IL-13 levels. We also showed that blocking NF-κB inhibited TRPA1 expression, and that blocking TRPA1 had no significant effect on the activation of NF-κB or TSLP expression. This study helps in understanding the role DINP exposure plays in the development of allergic dermatitis and provides new insight into the mechanisms behind the DINP-induced adjuvant effect.

Topics: Acetanilides; Animals; Cell Degranulation; Dermatitis, Allergic Contact; Disease Models, Animal; Disease Progression; Gene Expression Regulation; Immunohistochemistry; Male; Mast Cells; Mice; NF-kappa B; Phthalic Acids; Purines; Signal Transduction; Th2 Cells; TRPA1 Cation Channel

Several epidemiological studies have suggested a possible link between exposure to Diisononyl phthalate (DINP) and the development of allergies. These findings remain controversial since there is insufficient scientific evidence to assess the ability of DINP to influence allergic immune responses. In addition, the mechanisms behind DINP-caused allergic diseases have not been fully elucidated. In this study, Balb/c mice were orally exposed to DINP for 3 weeks and were then sensitized with fluorescein isothiocyanate (FITC). We showed that oral exposure to DINP could aggravate allergic-dermatitis-like lesions, indicated by an increase in the number of mast cells, and in increased skin edema in FITC-induced contact hypersensitivity. This deterioration was concomitant with increased total serum immunoglobulin-E and Th2 cytokines. We determined the oxidative damage and the activation of nuclear factor-kb (NF-kB). The data demonstrated that DINP could promote oxidative damage and the activation of NF-kB in the skin. The expression of thymic stromal lymphopoietin and the activation of signal transducer and activator of transcriptions 3, 5 and 6 were enhanced concomitant with exacerbated allergic dermatitis effects and the activation of NF-kB induced by DINP. These effects were alleviated by pyrollidine dithiocarbamate, an inhibitor of NF-kB. The results suggest that oral exposure to DINP aggravated allergic contact dermatitis, which was positively regulated via NF-kB.

Topics: Administration, Oral; Animals; Cytokines; Dermatitis, Allergic Contact; Disease Models, Animal; Dose-Response Relationship, Drug; Fluorescein-5-isothiocyanate; Immunoglobulin E; Male; Mice, Inbred BALB C; NF-kappa B; Oxidative Stress; Phthalic Acids; Pyrrolidines; Signal Transduction; Skin; STAT Transcription Factors; Th2 Cells; Thiocarbamates; Thymic Stromal Lymphopoietin