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.
Kim
Tae-Ho
TH
Department of Microbiology (BK21), College of Medicine, Kyung Hee University, Seoul 130701, Republic of Korea.
Jung
Jung-A
JA
Kim
Gun-Dong
GD
Jang
An-Hee
AH
Cho
Jeong-Je
JJ
Park
Yong Seek
YS
Park
Cheung-Seog
CS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000188:drug therapy*; D004139:Dinitrofluorobenzene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D015847:Interleukin-4; C012589:trichostatin A; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene