Exacerbated and prolonged allergic and non-allergic inflammatory cutaneous reaction in mice with targeted interleukin-18 expression in the skin
Exacerbated and prolonged allergic and non-allergic inflammatory cutaneous reaction in mice with targeted interleukin-18 expression in the skin
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DOI：
10.1046/j.1523-1747.2003.12407.x
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发表时间：
2003-09-01
影响因子：
6.5
通讯作者：
Yoshino, K
中科院分区：
文献类型：
--
作者：
Kawase, Y;Hoshino, T;Yoshino, K
白细胞介素18诱导T辅助细胞1和T辅助细胞2细胞因子、促炎细胞因子、趋化因子以及IgE和IgG 1产生。然而，白细胞介素18在炎症性皮肤反应中的作用仍不清楚。在这里，我们产生了角蛋白5/白细胞介素18转基因小鼠过度表达成熟的小鼠白细胞介素18在皮肤中使用的人角蛋白5启动子。在接触性超敏反应模型中，与对照同窝野生型或免疫球蛋白/白细胞介素18转基因小鼠相比，三硝基氯苯引起角蛋白5/白细胞介素18转基因小鼠更强的耳肿胀，其中成熟的白细胞介素18由免疫球蛋白启动子控制下的B和T细胞表达。应用刺激剂巴豆油，诱导角蛋白5/白细胞介素18转基因小鼠比免疫球蛋白/白细胞介素18转基因或野生型小鼠更强，更持久的耳肿胀。重复局部应用（每周一次，连续六周）的三硝基氯苯，他们的耳朵也引起了更强烈的皮肤炎症角蛋白5/白细胞介素18转基因小鼠比免疫球蛋白/白细胞介素18转基因或野生型小鼠。这六个三硝基氯苯应用后，干扰素-γ，白细胞介素-4，CCL 20 mRNA在耳组织中的表达增加，皮肤的变化，如棘皮和嗜酸性粒细胞，嗜酸性粒细胞和肥大细胞浸润，角蛋白5/白细胞介素18转基因小鼠比野生型小鼠更大。此外，重复应用引起角蛋白5/白细胞介素18转基因小鼠血清IgE水平和引流淋巴结中B细胞数量显着增加。这些结果表明，皮肤中白细胞介素18的过度表达加剧了过敏性和非过敏性皮肤炎症，这是伴随着皮肤中的T辅助细胞1和T辅助细胞2细胞因子和趋化因子的高表达。
Interleukin 18 induces both T helper 1 and T helper 2 cytokines, proinflammatory cytokines, chemokines, and IgE and IgG1 production. A role of interleukin 18 in inflammatory cutaneous reactions is still unclear, however. Here we generated keratin 5/interleukin 18 transgenic mice overexpressing mature murine interleukin 18 in the skin using a human keratin 5 promoter. In the contact hypersensitivity model, trinitrochlorobenzene elicited a stronger ear swelling in keratin 5/interleukin 18 transgenic mice compared with control littermate wild-type or immunoglobulin/interleukin 18 transgenic mice in which mature interleukin 18 was expressed by B and T cells under the control of the immunoglobulin promoter. Application of an irritant, croton oil, induced stronger and more sustained ear swelling in keratin 5/interleukin 18 transgenic mice than in immunoglobulin/ interleukin 18 transgenic or wild-type mice. Repetitive topical application ( weekly for six consecutive weeks) of trinitrochlorobenzene to their ears also elicited a stronger cutaneous inflammation in keratin 5/interleukin 18 transgenic mice than seen in immunoglobulin/ interleukin 18 transgenic or wild-type mice. After these six trinitrochlorobenzene applications, the expression of interferon-gamma, interleukin-4, and CCL20 mRNA in the ear tissue was increased and dermal changes, such as acanthosis and eosinophilic, neutrophilic, and mast cell infiltration, were greater in keratin 5/interleukin 18 transgenic mice than in wild-type mice. Furthermore, the repetitive application elicited a significant increase in serum IgE levels and the number of B cells in the draining lymph node in keratin 5/interleukin 18 transgenic mice. These results suggest that overexpression of interleukin 18 in the skin aggravates allergic and nonallergic cutaneous inflammation, which is accompanied by high expression of T helper 1 and T helper 2 cytokines and chemokines in the skin.