Thioredoxin Suppresses the Contact Hypersensitivity Response by Inhibiting Leukocyte Recruitment During the Elicitation Phase
Thioredoxin Suppresses the Contact Hypersensitivity Response by Inhibiting Leukocyte Recruitment During the Elicitation Phase
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DOI：
10.1089/ars.2008.2340
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发表时间：
2009-06-01
影响因子：
6.6
通讯作者：
Nishigori, Chikako
中科院分区：
文献类型：
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作者：
Fukunaga, Atsushi;Horikawa, Tatsuya;Nishigori, Chikako
硫氧还蛋白是一种氧化还原调节蛋白，清除活性氧，在治疗各种人类炎症性疾病的动物模型中显示出良好的抗炎效果。这项研究的目的是阐明硫氧还蛋白是否对治疗接触性皮炎等炎症性皮肤病有效，这些皮肤病是由皮肤表面暴露于环境和职业抗原引起的。硫氧还蛋白转基因小鼠的过敏性接触过敏反应被抑制。硫氧还蛋白的这种抑制作用似乎是通过抑制接触性超敏反应的传出肢体实现的，因为给予重组硫氧还蛋白抑制了诱发期的炎症反应，但不能抑制诱导期的炎症反应。过继转移研究表明，宿主环境，而不是供者白细胞，在这种抑制作用中起关键作用。在硫氧还蛋白转基因小鼠中，中性粒细胞在激发部位的渗透减少，而皮肤树突状细胞的迁移功能和半抗原特异性细胞的增殖没有受到干扰。硫氧还蛋白转基因小鼠对巴豆油的炎症反应也有所减弱。这些发现表明，硫氧还蛋白可以预防皮肤炎症反应，可能是治疗接触性皮炎的合适候选药物。抗氧化剂。氧化还原信号。11,1227-1235。
Thioredoxin, a redox-regulating protein that scavenges reactive oxygen species, appears to show an excellent antiinflammatory effect in treating animal models of various human inflammatory diseases. The aim of this study was to clarify whether thioredoxin is useful for treating inflammatory skin diseases, such as contact dermatitis, caused by epicutaneous exposure to environmental and occupational antigens. The allergic contact hypersensitivity response was suppressed in thioredoxin-transgenic mice. This suppressive effect of thioredoxin appeared to be via the inhibition of the efferent limb of contact hypersensitivity because administration of recombinant thioredoxin suppressed the inflammatory response in the elicitation phase but not in the induction phase. Adoptive-transfer studies revealed that the host environment, but not donor leukocytes, is critical in this suppressive effect. In thioredoxin-transgenic mice, the infiltration of neutrophils in the elicitation site was diminished, whereas the migratory function of cutaneous dendritic cells and hapten-specific cell proliferation were not disturbed. Thioredoxin-transgenic mice had also an attenuated inflammatory response to croton oil. These findings suggest that thioredoxin prevents skin inflammatory responses and could be a suitable candidate for the treatment of contact dermatitis. Antioxid. Redox Signal. 11, 1227-1235.