PMID- 22944277
OWN - NLM
STAT- MEDLINE
DCOM- 20130909
LR  - 20120904
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 92
IP  - 28
DP  - 2012 Jul 24
TI  - [Inhibition of elicitation of allergic contact dermatitis by topical use of 
      Z-VAD-FMK, a broad caspase inhibitor: experiment in mice].
PG  - 1992-6
AB  - OBJECTIVE: To explore the effects of 
      N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), a broad caspase 
      inhibitor, on the elicitation of murine allergic contact dermatitis (ACD) and 
      examine the effects on T lymphocytes. METHODS: 1-fluoro-2,4-dinitrobenzene (DNFB) 
      was used to establish the classical murine model of ACD. Different concentrations 
      of Z-VAD-FMK were applied before ear provocation. Several parameters were 
      detected, including ear swelling degree, weight differences and thickness of ear 
      tissue under microscope between 2 ears. Enzyme-linked immunosorbent assay (ELISA) 
      was used to detect the levels of Th1 cytokines (INF-gamma and IL-2) in ear tissues. 
      Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to 
      detect their levels of mRNA and the results were shown as "copies relative to one 
      million housekeeping genes". Local lymph node assay (LLNA) was conducted. 
      Bromodeoxyuridine-flow cytometry was used to detect the proliferation of T 
      lymphocytes in local lymph node and flow cytometry to detect the activation of T 
      lymphocytes. RESULTS: The right ear swelling degree, weight differences and 
      thickness between two ears in the 1.25 mmol/L Z-VAD-FMK group were (12.6 +/- 
      1.2)x10(-2) mm, (3.1 +/- 0.2) mg, and (12.1 +/- 1.1)x10(-2) mm respectively. And they 
      were all significantly lower than those of the negative control group((17.4 +/- 
      1.6)x10(-2) mm, (4.2 +/- 0.3) mg, (16.7 +/- 1.5)x10(-2) mm;q = 3.25, 2.98, 3.12, all 
      P < 0.05). The levels of INF-gamma and IL-2 in the ear skin lesions of 1.25 mmol/L 
      Z-VAD-FMK group were (856 +/- 45) and (167 +/- 12) pg/ml respectively and they were 
      both significantly lower than those of the negative control group ((1180 +/- 58) 
      and (225 +/- 16) pg/ml; q = 3.11, 3.14, both P < 0.05). The mRNA levels of the 
      above two cytokines were 152 +/- 12 and 96 +/- 8 respectively and they were both 
      significantly lower than those of the negative control group (220 +/- 15 and 156 +/- 
      11;q = 3.15, 3.42, both P < 0.05). In LLNA, the mean intensity of BrdU in T 
      lymphocytes of 1.25 mmol/L Z-VAD-FMK-treated group was significantly weaker than 
      that of the negative control group (185 +/- 15 vs 298 +/- 21, q = 3.02, P < 0.05). 
      The percent of activation markers-positive T lymphocytes of the Z-VAD-FMK group 
      were 7.8% +/- 0.7%, 9.8% +/- 0.8% and 31.2% +/- 2.8% respectively and they were all 
      significantly lower than those of the negative control group (10.5% +/- 1.0%, 14.5% 
      +/- 1.1%, 46.5% +/- 3.2%, q = 3.16, 3.52, 3.11, all P < 0.05). CONCLUSION: Topical 
      use of Z-VAD-FMK prior to ear provocation can suppress the proliferation and 
      activation of T lymphocytes in both skin tissues and local lymph nodes and thus 
      result in the inhibitory effect of allergic contact dermatitis.
FAU - Li, Yuan-yuan
AU  - Li YY
AD  - Department of Dermatology, Shandong University, Jinan, China.
FAU - Yan, Chun-lin
AU  - Yan CL
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/*pharmacology/therapeutic use
MH  - Animals
MH  - Caspase Inhibitors/*pharmacology/therapeutic use
MH  - Dermatitis, Allergic Contact/immunology/*prevention & control
MH  - Female
MH  - Lymphocyte Activation/*drug effects/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - T-Lymphocytes/*drug effects/immunology
EDAT- 2012/09/05 06:00
MHDA- 2013/09/10 06:00
CRDT- 2012/09/05 06:00
PHST- 2012/09/05 06:00 [entrez]
PHST- 2012/09/05 06:00 [pubmed]
PHST- 2013/09/10 06:00 [medline]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2012 Jul 24;92(28):1992-6.