The histone deacetylase inhibitor, trichostatin A, inhibits the development of 2,4-dinitrofluorobenzene-induced dermatitis in NC/Nga mice

Repetitive skin contact with a chemical hapten like 2,4-dinitrofluorobenzene (DNFB) evokes an atopic dermatitis (AD)-like dermatitis reaction in NC/Nga mice maintained under specific pathogen-free (SPF) conditions. The histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), modulates the expression of several genes by inhibiting the activity of HDACs. Furthermore, TSA has been reported to suppress inflammatory cytokine expression and to induce T cell-suppression by increasing regulatory T cell (T reg cell) numbers. In addition, histone deacetylase inhibitors (HDACi) are currently undergoing clinical trials for the treatment of inflammatory disorders.In the present study, we examined whether treatment with TSA suppresses AD-like skin lesions in NC/Nga mice treated with DNFB under SPF conditions. Intraperitoneal (i.p.) administration of TSA to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. Furthermore, IL-4 production by CD4+ T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by TSA, although levels of IFN-γ were not. Flow cytometric analysis of lymphocytes showed an increase in CD4+ CD25+ T cell proportions in mice given TSA-i.p. These findings suggest that TSA suppresses the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IL-4 production and increasing the T reg cell population.

Research Highlights
► Trichostatin A reduced IL-4 levels after TCR stimulation in CD4+T cells.
► Trichostatin A inhibited the DNFB-induced infiltration of inflammatory cells into ear lobes.
► Trichostatin A ameliorated Atopic dermatitis-like skin lesions.