Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
Toxicology. 2019 Jan 15;412:48-54. doi: 10.1016/j.tox.2018.11.014. Epub 2018 Nov 29.
The prevalence of skin allergies could be partly due to the increased exposure to chemicals from consumer products. Chemicals that can enhance hypersensitivity caused by other chemicals are the focus of this study. We have demonstrated that phthalate esters with short chain alcohols enhance fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) in a mouse model. We have also found that tributyrin, a triacylglycerol (TAG) with three butyric acids, enhances sensitization to FITC. To elucidate such an enhanced skin sensitization might be based on a general feature of TAG, we compared tributyrin and triolein, a natural TAG, as to an adjuvant effect on FITC-CHS. Triolein is the dominant TAG in olive oil and contains long chain mono-unsaturated fatty acids. Unlike tributyrin and dibutyl phthalate (DBP), triolein did not exhibit an adjuvant effect. With triolein, enhancement of FITC-presenting CD11c dendritic cell trafficking to draining lymph nodes was weak, and the activation status of DC, as revealed as CD86 expression, was low. We found a difference in the pattern of skin cytokine production, i.e., that thymic stromal lymphopoietin was produced with DBP and interleukin-1β with tributyrin. Triolein did not induce either of these cytokines. This illustrates that the adjuvant effect of tributyrin on FITC-CHS is not a general phenomenon for TAGs. Although beneficial effects may be expected through oral administration of tributyrin, the effect on skin immune systems should be considered.
皮肤过敏的流行可能部分归因于人们接触到更多的消费品化学物质。本研究关注的是能够增强其他化学物质引起的超敏反应的化学物质。我们已经证明，短链醇类邻苯二甲酸酯能够增强小鼠模型中荧光素异硫氰酸酯（FITC）诱导的接触超敏反应（CHS）。我们还发现，三丁酸甘油酯，一种含有三个丁酸的三酰基甘油（TAG），能够增强对 FITC 的致敏作用。为了阐明这种增强的皮肤致敏作用是否基于 TAG 的一般特征，我们比较了三丁酸甘油酯和三油酸甘油酯，一种天然的 TAG，作为 FITC-CHS 的佐剂作用。三油酸甘油酯是橄榄油中的主要 TAG，并且含有长链单不饱和脂肪酸。与三丁酸甘油酯和邻苯二甲酸二丁酯（DBP）不同，三油酸甘油酯没有表现出佐剂作用。用三油酸甘油酯时，向引流淋巴结输送 FITC 呈递 CD11c 树突状细胞的增强作用较弱，并且 DC 的激活状态，如 CD86 表达，较低。我们发现皮肤细胞因子产生模式存在差异，即 DBP 产生胸腺基质淋巴细胞生成素，三丁酸甘油酯产生白细胞介素-1β。三油酸甘油酯没有诱导这两种细胞因子。这表明，三丁酸甘油酯对 FITC-CHS 的佐剂作用不是 TAG 的普遍现象。虽然通过口服三丁酸甘油酯可能会产生有益的效果，但应考虑其对皮肤免疫系统的影响。
