[Attenuation of allergic contact dermatitis by Z-VAD-FMK, a broad caspase inhibitor: experiment with mice].
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].


CONCLUSIONS
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.
Li
Yuan-Yuan
YY
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Yan
Chun-Lin
CL
Xu
Wei
W
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone