Elder J T, Cromie M A, Griffiths C E, Chambon P, Voorhees J J
Department of Dermatology, University of Michigan, Ann Arbor 48109-0672.
J Invest Dermatol. 1993 Apr;100(4):356-9. doi: 10.1111/1523-1747.ep12471816.
Acute topical treatment of human skin with retinoic acid (RA) results in a pleiotropic response, some aspects of which are mimicked by non-specific irritants. To identify reliable cutaneous markers of retinoid action, it is important to determine which aspects of this response are specifically due to the presence of RA. We have previously demonstrated a rapid and pronounced increase in steady-state cellular RA-binding protein II (CRABP-II)mRNA levels after topical RA treatment. Here we characterize the dose dependence and kinetics of this response, and compare the effects of a well-known irritant, sodium dodecylsulfate (SDS), to those of RA and its vehicle. The induction of CRABP-II mRNA in response to 0.1% RA cream was maximal by 16 h (elevenfold relative to untreated skin), and persisted at near-maximal levels (eight-fold) for up to 4 d. RA was potent in eliciting this response, as approximately half-maximal stimulation was observed after 16 h of treatment with 0.001% RA. Treatment for 4 d with 0.1% RA cream versus 2% SDS in RA vehicle resulted in nearly identical levels of cutaneous erythema, spongiosis, and epidermal thickening. However, the CRABP-II mRNA response to 2% SDS was no greater than that observed in response to vehicle alone (2.9 times relative to occluded skin control at 4 d). SDS also had no effect upon either CRABP-II or RAR-beta mRNA levels in quiescent human dermal fibroblasts in vitro, whereas RA elicited both responses at 1000-times lower concentrations than SDS. Taken together, these data identify the CRABP-II mRNA response as a reliable, rapid, and selective marker for retinoid activity in human skin.
用维甲酸（RA）对人体皮肤进行急性局部治疗会产生多效性反应，其中一些方面可被非特异性刺激物模拟。为了确定维甲酸作用的可靠皮肤标志物，确定这种反应的哪些方面是由RA的存在特异性引起的很重要。我们之前已经证明，局部应用RA后，稳态细胞RA结合蛋白II（CRABP-II）mRNA水平会迅速且显著升高。在此，我们描述了这种反应的剂量依赖性和动力学，并将一种知名刺激物十二烷基硫酸钠（SDS）的作用与RA及其赋形剂的作用进行比较。对0.1%RA乳膏的反应中，CRABP-II mRNA的诱导在16小时时达到最大值（相对于未处理皮肤增加了11倍），并在接近最大值的水平（8倍）持续长达4天。RA在引发这种反应方面很有效，因为用0.001%RA处理16小时后观察到约半数最大刺激。在RA赋形剂中用0.1%RA乳膏与2%SDS处理4天，导致皮肤红斑、海绵形成和表皮增厚的水平几乎相同。然而，CRABP-II mRNA对2%SDS的反应不大于对单独赋形剂的反应（相对于4天时封闭皮肤对照增加2.9倍）。SDS对体外静止的人皮肤成纤维细胞中的CRABP-II或RAR-β mRNA水平也没有影响，而RA在比SDS低1000倍的浓度下就能引发这两种反应。综上所述，这些数据确定CRABP-II mRNA反应是人体皮肤中维甲酸活性的可靠、快速和选择性标志物。
