Effect of Am-80, a retinoid derivative, on 2, 4-dinitrofluorobenzene-induced contact dermatitis in mice.
Retinoids have many pharmacological activities, including anti-inflammatory action and antiangiogenesis, effected through the regulation of various gene transcriptions. In this study, we investigated the effect of Am-80, one of the retinoic acid derivatives, on hapten-induced contact hypersensitivity in BALB/c mice. After application of 2,4-dinitrofluorobenzene (DNFB) to the ears of the mice, severe contact hypersensitivity with marked infiltration of inflammatory cells and hypertrophy of the epidermis was caused. The thickness of the ears increased biphasically and reached a peak 3 and 24 h after the DNFB challenge. Am-80 significantly inhibited ear thickness in the late-(24 h), but not the early-phase (3 h) reaction in a dose-dependent manner. In a histopathological study, obvious depression of edema and infiltration of inflammatory cells was observed in the ears of mice treated with Am-80. Am-80 inhibited the levels of expression in mice ears of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6), but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). Furthermore, Am-80 inhibited the antigen-induced production of some cytokines, including IFN-gamma and IL-6, but not IL-4, in vitro. Therefore, Am-80 inhibited hapten-induced contact hypersensitivity through the direct inhibition of inflammatory cytokines such as IFN-gamma and IL-6.
Niwa
S
S
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Ochi
T
T
Hirano
Y
Y
Wang
T
T
Inagaki
N
N
Shudo
K
K
Nagai
H
H
D000818:Animals; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D003877:Dermatitis, Contact / Q000188:drug therapy*; D004139:Dinitrofluorobenzene; D005260:Female; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology / Q000627:therapeutic use*
D001565:Benzoates; D015850:Interleukin-6; D012333:RNA, Messenger; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene