Chymase Inhibitor Improves Dermatitis in NC/Nga Mice
Chymase Inhibitor Improves Dermatitis in NC/Nga Mice
复制标题
食糜酶抑制剂可改善 NC/Nga 小鼠的皮炎
DOI：
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发表时间：
2002
影响因子：
2.8
通讯作者：
Y. Fukuda
中科院分区：
文献类型：
--
作者：
N. Watanabe;Y. Tomimori;Kayo Saito;Kenju Miura;Adumi Wada;M. Tsudzuki;Y. Fukuda
背景：肥大细胞糜酶被认为参与变态反应性炎症，但其确切作用尚不清楚。近亲交配的NC/NGA小鼠在传统环境中长大后会出现类似于特应性皮炎(AD)的皮肤病变。为了阐明糜酶在AD中的可能作用，我们检测了一种糜酶抑制剂对NC/NGA小鼠皮损的影响。方法：NC/NGA小鼠每天灌胃糜酶抑制剂SUN-C8257 150 mg/kg/d，在实验第35天评价皮炎的严重程度。用重组小鼠肥大细胞蛋白-4(mMCP-4)在体内外进一步研究了糜酶在皮炎中的作用。结果：SUN-C8257可显著降低NC/NGA小鼠的临床皮肤和组织学评分。Sun-C8257还抑制了炎症细胞的聚集，如嗜酸性粒细胞和肥大细胞，在该模型中受影响的皮损中。MMCP-4在体外刺激嗜酸性粒细胞迁移，皮内注射该酶导致包括嗜酸性粒细胞在内的炎性细胞在注射部位显著聚集。因此，SUN-C8257对NC/NGA小鼠皮损的改善可能至少部分是由于抑制了皮损中的细胞浸润。结论：肥大细胞糜酶可能参与了AD的发病机制，SUN-C8257将有助于AD的治疗。
Background: Mast cell chymase is thought to participate in allergic inflammation, but its precise role remains undetermined. Inbred NC/Nga mice develop skin lesions similar to atopic dermatitis (AD) when they grow up in a conventional environment. To elucidate the possible role of chymase in AD, we examined the effect of a chymase inhibitor on skin lesions of NC/Nga mice. Methods: NC/Nga mice were given the chymase inhibitor SUN-C8257 daily at 150 mg/kg/day with drinking water, and the severity of the dermatitis was evaluated on day 35 of the experiment. The role of chymase in dermatitis was further investigated in vitro and in vivo using recombinant mouse mast cell protease-4 (mMCP-4). Results: Administration of SUN-C8257 significantly reduced the clinical skin and histological score in NC/Nga mice. SUN-C8257 also inhibited the accumulation of inflammatory cells, such as eosinophils and mast cells, in the affected lesions in this model. mMCP-4 stimulated eosinophil migration in vitro, and intradermal injection of the enzyme resulted in a significant accumulation of inflammatory cells, including eosinophils, at the injection site. Thus amelioration of the skin lesions in NC/Nga mice by SUN-C8257 might be, at least in part, due to the suppression of cell infiltration in the lesions. Conclusions: Mast cell chymase may contribute to the pathogenesis of AD, and SUN-C8257 will be beneficial to the treatment of the skin disorder.
DOI：
10.1073/pnas.85.12.4460
发表时间：
1988-06-01
影响因子：
11.1
作者：
WATANABE, N;KATAKURA, K;OVARY, Z
通讯作者：
OVARY, Z
影响因子：
14.2
作者：
LEUNG, DYM;HIRSCH, RL;HANIFIN, JM
通讯作者：
HANIFIN, JM
DOI：
10.1073/pnas.94.17.9017
发表时间：
1997-08-19
影响因子：
11.1
作者：
Longley, BJ;Tyrrell, L;Schechter, NM
通讯作者：
Schechter, NM