Hurks H M, Out-Luiting C, Van den Molen R G, Vermeer B J, Claas F H, Mommaas A M
Department of Dermatology, University Hospital Leiden, The Netherlands.
Photochem Photobiol. 1997 Apr;65(4):616-21. doi: 10.1111/j.1751-1097.1997.tb01902.x.
Cis-urocanic acid (UCA), formed in the stratum corneum by UV irradiation of trans-UCA has been proposed as a mediator of UV-induced immunosuppression in the skin. In this study, we examined the in vitro effect of cis-UCA (6-100 micrograms/mL) on the human mixed lymphocyte reaction (MLR) and the mixed epidermal cell lymphocyte reaction (MECLR). Addition of cis-UCA (purified or in a mixture with trans-UCA) did not affect the MLR but was able to induce a 20% suppression of the MECLR responses. Because this effect of cis-UCA on the MECLR was not as strong as could be expected from previous in vivo results, we designed a set of experiments in order to enhance the in vitro immunosuppressive capacity of cis-UCA. Firstly, we preincubated epidermal cells with UCA (50 micrograms/mL). for 3 or 6 days before culture in the MECLR because in vivo repeated UV exposure can lead to a photostationary state, where cis-UCA may be present for several weeks. This pretreatment with cis-UCA resulted in a maximal decrease of the MECLR response of 27%, whereas trans-UCA had no effect. Secondly, we investigated whether UVB irradiation of epidermal cells could make cells more sensitive to cis-UCA. However, addition of trans- or cis-UCA did not potentiate the reduced alloactivating capacity of UVB-irradiated cells. Finally, we examined the possibility of a synergistic effect of cis-UCA with histamine. Addition of histamine suppressed the MLR and MECLR responses, but neither cis- nor trans-UCA were able to modulate this decrease. We conclude that cis-UCA can partly downregulate the human MECLR but not the MLR. The mechanism involved in this differential downregulation is not known. In this respect it is striking that cis-UCA dose not potentiate the UVB- or histamine-induced suppression of the MECLR.
顺式尿刊酸（UCA）由反式UCA经紫外线照射在角质层中形成，被认为是皮肤中紫外线诱导免疫抑制的介质。在本研究中，我们检测了顺式UCA（6 - 100微克/毫升）对人混合淋巴细胞反应（MLR）和混合表皮细胞淋巴细胞反应（MECLR）的体外作用。添加顺式UCA（纯化的或与反式UCA混合）不影响MLR，但能够诱导MECLR反应抑制20%。由于顺式UCA对MECLR的这种作用不如先前体内实验结果所预期的那么强，我们设计了一组实验以增强顺式UCA的体外免疫抑制能力。首先，我们在MECLR培养前，用UCA（50微克/毫升）预孵育表皮细胞3天或6天，因为体内反复紫外线照射可导致光稳态，此时顺式UCA可能会存在数周。这种用顺式UCA预处理导致MECLR反应最大降低27%，而反式UCA则无作用。其次，我们研究了表皮细胞的UVB照射是否会使细胞对顺式UCA更敏感。然而，添加反式或顺式UCA并不能增强UVB照射细胞降低的同种异体激活能力。最后，我们检测了顺式UCA与组胺协同作用的可能性。添加组胺可抑制MLR和MECLR反应，但顺式和反式UCA均不能调节这种降低。我们得出结论，顺式UCA可部分下调人MECLR，但不能下调MLR。这种差异下调所涉及的机制尚不清楚。在这方面，顺式UCA不能增强UVB或组胺诱导的MECLR抑制作用这一点很引人注目。
