Antagonism of epidermal growth factor receptor tyrosine kinase ameliorates the psoriatic phenotype in organ-cultured skin.
Antagonism of epidermal growth factor receptor tyrosine kinase ameliorates the psoriatic phenotype in organ-cultured skin.
复制标题
表皮生长因子受体酪氨酸激酶的拮抗作用可改善器官培养皮肤的银屑病表型。
DOI：
10.1159/000084909
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Elder,JT
中科院分区：
文献类型：
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作者：
Varani,J;Lateef,H;Fay,K;Elder,JT
银屑病斑块皮肤在器官培养物中培养8天，在有效的表皮生长因子（EGF）受体酪氨酸激酶（RTK）拮抗剂的存在下恢复到更正常的组织学外观，而未经治疗的银屑病斑块皮肤保留与银屑病表型相关的组织学特征。在伴随研究中，显示EGF-RTK拮抗剂对非银屑病皮肤的组织学特征没有显著影响，对真皮功能没有影响，即对I型前胶原和基质金属蛋白酶-1（MMP-1;间质胶原酶）的加工。当在单层培养中用EGF-RTK拮抗剂处理人表皮角质形成细胞时，观察到生长抑制（ED 50 =约0.06 µM）。当真皮成纤维细胞在单层培养中暴露于EGF-RTK拮抗剂时，在干扰角质形成细胞生长的浓度（高达1 µM）下，增殖、MMP-1和I型前胶原的产生基本上不受影响。EGF-RTK拮抗剂在正常皮肤结构和真皮功能基本不受影响的条件下调节器官培养中银屑病皮肤的组织学特征的能力表明了抗银屑病治疗的潜力。
Psoriatic plaque skin incubated for eight days in organ culture in the presence of a potent epidermal growth factor (EGF) receptor tyrosine kinase (RTK) antagonist reverted to a more normal histological appearance, while untreated psoriatic plaque skin retained histological features associated with the psoriatic phenotype. In concomitant studies it was shown that the EGF-RTK antagonist had no significant effect on histological features of non-psoriatic skin and no effect on dermal function, i.e. elaboration of both type I procollagen and matrix metalloproteinase-1 (MMP-1; interstitial collagenase). When human epidermal keratinocytes were treated with the EGF-RTK antagonist in monolayer culture, growth inhibition was seen (ED50= approximately 0.06 µM). When dermal fibroblasts were exposed to the EGF-RTK antagonist in monolayer culture, proliferation, MMP-1 and type I procollagen production were essentially unaffected at concentrations which interfered with keratinocyte growth (up to 1 µM). The capacity of the EGF-RTK antagonist to modulate the histological features of psoriatic skin in organ culture under conditions in which normal skin architecture and dermal function are largely unaffected suggests a potential for anti-psoriatic therapy.