Zhonghua yi xue za zhi · 2008
[Attenuation of allergic contact dermatitis by Z-VAD-FMK, a broad caspase inhibitor: experiment with mice].
Аннотация на английскомСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Li Yuan-Yuan, Yan Chun-Lin, Xu Wei
Аннотация
OBJECTIVE: To investigate the effects of N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), a broad caspase inhibitor, on allergic contact dermatitis (ACD).
METHODS: A Balb/c mouse was killed and its back skin was peeled, put into a Franz diffusion cell, and smeared with Z-VAD-FMK. High performance liquid chromatography was used to examine the permeation rate. Dinitro-fluorobenzene (DNFB) was applied on the depilated back of mice as inducer and then on the back-side of right ear as provocative agent 6 days later so as to establish mouse ACD models. Two hours after the provocation 24 mouse models were divided into 4 equal groups to undergo the application of Z-VAD-FMK at the concentration of 0.1, 0.5, 2.5, and 5 mmol/L on the back-side of right ear twice. PBS was applied in the negative control group. Then the mice were killed with their 2 ears cut off. Microscopy was used to measure the right ear swelling degree, and differences in weight and thickness between the 2 ears. ELISA was used to detect the levels of IL-2 and INF-gamma in the ear tissues.
RESULTS: The transdermal permeation rates of Z-VAD-FMK at the time points 6, 12, and 24 h were 2.15%, 9.62%, and 12.85% respectively. The right ear swelling degree, and differences in weight and thickness between the 2 ears in the 2.5 mmol/L Z-VAD-FMK group were (12.5 +/- 1.4) x 10(-2) mm, (3.2 +/- 0.3) mg, and (11.8 +/- 1.3) x 10(-2) mm respectively, all significantly lower than those of the negative control group [(19.1 +/- 2.0) x 10(-2) mm, (4.3 +/- 0.4) mg, and (16.8 +/- 1.7) x 10(-2) mm, all P < 0.05]. The IL-2 and INF-gamma levels in the ear skin lesion of the 2.5 mmol/L Z-VAD-FMK group were (148 +/- 10) and (650 +/- 45) pg/ml respectively, both significantly lower than those of the negative control group [(205 +/- 18) and (1030 +/- 58) pg/ml, both P < 0.05].
CONCLUSION: Z-VAD-FMK can permeate through mouse skin and inhibit the activation and proliferation of T lymphocytes, leading to the inhibitory effect of contact allergic reaction.
METHODS: A Balb/c mouse was killed and its back skin was peeled, put into a Franz diffusion cell, and smeared with Z-VAD-FMK. High performance liquid chromatography was used to examine the permeation rate. Dinitro-fluorobenzene (DNFB) was applied on the depilated back of mice as inducer and then on the back-side of right ear as provocative agent 6 days later so as to establish mouse ACD models. Two hours after the provocation 24 mouse models were divided into 4 equal groups to undergo the application of Z-VAD-FMK at the concentration of 0.1, 0.5, 2.5, and 5 mmol/L on the back-side of right ear twice. PBS was applied in the negative control group. Then the mice were killed with their 2 ears cut off. Microscopy was used to measure the right ear swelling degree, and differences in weight and thickness between the 2 ears. ELISA was used to detect the levels of IL-2 and INF-gamma in the ear tissues.
RESULTS: The transdermal permeation rates of Z-VAD-FMK at the time points 6, 12, and 24 h were 2.15%, 9.62%, and 12.85% respectively. The right ear swelling degree, and differences in weight and thickness between the 2 ears in the 2.5 mmol/L Z-VAD-FMK group were (12.5 +/- 1.4) x 10(-2) mm, (3.2 +/- 0.3) mg, and (11.8 +/- 1.3) x 10(-2) mm respectively, all significantly lower than those of the negative control group [(19.1 +/- 2.0) x 10(-2) mm, (4.3 +/- 0.4) mg, and (16.8 +/- 1.7) x 10(-2) mm, all P < 0.05]. The IL-2 and INF-gamma levels in the ear skin lesion of the 2.5 mmol/L Z-VAD-FMK group were (148 +/- 10) and (650 +/- 45) pg/ml respectively, both significantly lower than those of the negative control group [(205 +/- 18) and (1030 +/- 58) pg/ml, both P < 0.05].
CONCLUSION: Z-VAD-FMK can permeate through mouse skin and inhibit the activation and proliferation of T lymphocytes, leading to the inhibitory effect of contact allergic reaction.