Molecular mechanisms of cis-urocanic acid and permethrin-induced alterations in cutaneous immunity.
Molecular mechanisms of cis-urocanic acid and permethrin-induced alterations in cutaneous immunity.
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顺式尿刊酸和氯菊酯诱导皮肤免疫改变的分子机制。
DOI：
10.1046/j.1600-0781.2003.00058.x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Holladay,SD
中科院分区：
文献类型：
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作者：
Prater,MR;Blaylock,BL;Holladay,SD
背景/目的：皮肤尿酸（cUCA）或紫外线B暴露已被证明可导致小鼠皮肤接触超敏反应（CH）减少并诱导全身耐受性（调节性T淋巴细胞增加）。氯菊酯也是一种已知的CH抑制剂，但其分子机制目前尚不清楚。在这项研究中，研究人员在四种小鼠中对CH进行了评估：免疫敏感株（C57BL/6N），免疫抗性株（SvImJ），从C57BL/6N小鼠中培养的菌株，但在肿瘤坏死因子α受体（TNFαp55R和p75R）上都发生了基因改变，以及从C57BL/6N培养的菌株，但在干扰素γ (IFNγ)位点上基因缺失。方法：在5周龄的雌性C57BL/6N、SvImJ和C57BL/6N小鼠中，在TNFα或IFNγ位点发生基因改变后，通过恶唑酮刺激5天暴露于皮内（ID） cUCA或单次暴露于局部氯菊酯，或同时暴露于这两种化学物质，对每组的CH进行评估。结果：在C57BL/6N小鼠中，5天暴露于氯菊酯或单次局部暴露于氯菊酯会导致CH反应减弱，同时暴露于这两种化学物质会加剧这种影响。相对于C57BL/6N小鼠，SvImJ中的CH对氯氰菊酯和氯氰菊酯都具有抗性，因为5天的氯氰菊酯或单次暴露不会减少CH，同时暴露于氯氰菊酯和氯氰菊酯也不会减少CH。两个TNFαR基因位点缺失的小鼠对氯氰菊酯或氯菊酯表现出相似但有所减弱的CH减少反应。这一趋势在综合化学物质暴露中变得明显。IFNγ敲除小鼠对cUCA或氯菊酯单独表现出类似的CH减少反应。与C57BL/6N小鼠不同，IFNγ敲除小鼠在联合化学暴露下没有显示CH的进一步减少。结论：小鼠品系对氯菊酯和cUCA诱导的免疫调节表现出不同的敏感性。2TNFα可能参与了氯氰菊酯和氯菊酯的免疫调节作用。ccu +氯菊酯对CH的抑制作用可能需要3IFNγ的参与。
Background/Purpose:Cutaneouscis‐urocanic acid (cUCA) or ultraviolet B exposure has been shown to cause diminished cutaneous contact hypersensitivity (CH) and to induce systemic tolerance (increased regulatory T lymphocytes) in mice. Permethrin is also a known CH inhibitor, but the molecular mechanisms are currently poorly understood. In this study, CH was evaluated in four strains of mice: an immunosensitive strain (C57BL/6N), an immunoresistant strain (SvImJ), a strain developed from C57BL/6N mice but genetically altered at both the tumor necrosis factor‐alpha receptors (TNFαp55R and p75R), and a strain developed from C57BL/6N but genetically deleted at the interferon‐gamma (IFNγ) locus.Methods:CH was evaluated in each group via oxazolone challenge following a 5‐day exposure to intradermal (ID) cUCA or a single exposure to topical permethrin, or co‐exposure to both chemicals in 5‐week‐old female C57BL/6N, SvImJ, and C57BL/6N mice genetically altered at the TNFα or IFNγ locus.Results:A 5‐day exposure to ID cUCA or a single exposure to topical permethrin resulted in diminished CH response in C57BL/6N mice, and this effect was exacerbated with concurrent exposure to both chemicals. CH in SvImJ was both cUCA‐ and permethrin‐resistant relative to C57BL/6N mice, as 5‐day cUCA or a single exposure to permethrin did not diminish CH, nor did concurrent exposure to cUCA and permethrin. Mice deleted at both TNFαR loci displayed similar but somewhat blunted diminished CH responses to cUCA or permethrin. This trend became significant with combined chemical exposure. IFNγ knockout mice displayed similar diminished CH responses to cUCA or permethrin alone. Unlike C57BL/6N mice, the IFNγ knockout mice did not show a further reduction in CH with combined chemical exposure.Conclusions:These results suggest the following:1Mouse strains show variable susceptibility to permethrin‐ and cUCA‐induced immunomodulation.2TNFα may be involved in the immunomodulatory effects of cUCA and permethrin.3IFNγ may be required for the more than additive depression of CH caused by cUCA+permethrin.