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首页> 外文期刊>Journal of applied toxicology >Allergen-induced changes in interleukin 1 beta (IL-1 beta) mRNA expression by human blood-derived dendritic cells: inter-individual differences and relevance for sensitization testing.
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Allergen-induced changes in interleukin 1 beta (IL-1 beta) mRNA expression by human blood-derived dendritic cells: inter-individual differences and relevance for sensitization testing.

机译：变应原诱导的人血源性树突状细胞白介素1 beta（IL-1 beta）mRNA表达的变化：个体差异和致敏性测试的相关性。

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The development of in vitro methods for the identification of skin sensitizers based upon analysis of Langerhans cell (LC) function has been constrained by the fact that these cells represent only a minority population in the skin that, once isolated, alter their phenotype spontaneously and rapidly. Methods have been developed recently that allow the expansion in culture using appropriate cytokine conditions of LC-like dendritic cells (DCs) from certain tissues, including human peripheral blood. It has been demonstrated that culture of human blood-derived LC-like cells with selected potent contact allergens such as 2,4-dinitrofluorobenzene (DNFB) stimulates selective phenotypic changes, including the up-regulation of interleukin 1 beta (IL-1 beta) mRNA expression, under conditions where skin irritants are without effect. However, in our own previous investigations, we have observed that there appear to be differences between blood donors with respect to the responsiveness of DCs to DNFB-induced changes in IL-1 beta expression, differences that could compromise the utility of this approach as a screening method for contact allergens. We have therefore investigated donor variability in DC responsiveness to a panel of known human contact allergens (DNFB; paraphenylene diamine, PPD; methyl- chloroisothiazolinone/methylisothiazolinone, CMIT), to the skin irritant benzalkonium chloride and to the mitogen phorbol myristate acetate (PMA). Dendritic cells derived from all donors expressed IL-1 beta mRNA constitutively. Treatment of DCs isolated from donors with a responder phenotype to DNFB with PPD or CMIT resulted also in up-regulation of IL-1 beta mRNA expression, although such changes were always comparatively modest, generally resulting in a twofold induction compared with vehicle-treated controls. Dendritic cells derived from donors with a non-responder phenotype to DNFB failed also to respond to these additional contact allergens under conditions where the mitogen PMA caused similar increases in IL-1 beta expression to those observed for allergen-responsive donors. Benzalkonium chloride failed to provoke changes in the expression of this cytokine in any donor examined, irrespective of their responder phenotype. The temporal stability of the responderon-responder DC phenotype was confirmed, with stable phenotypes with respect to DNFB-induced changes in IL-1 beta mRNA expression observed over a period of some 18 months. Fifty per cent (6/12) of donors tested over this period displayed a responder phenotype. These data demonstrate that chemical allergens do stimulate consistent changes in IL-1 beta mRNA expression in the proportion of donors who have a responsive phenotype, and that such responses are apparently selective for allergen using the relatively narrow range of materials assessed to date. However, the modest response to very strong contact allergens, coupled with the difficulties of responderon-responder phenotypes, means that in its present form this approach does not lend itself to the routine assessment of skin sensitizing activity. Copyright 2001 John Wiley & Sons, Ltd.
机译：由于这些细胞仅代表皮肤中的少数群体，一旦分离，它们会自发迅速地改变其表型，因此，已经限制了基于朗格罕斯细胞（LC）功能分析的鉴定皮肤敏化剂的体外方法的发展。 。最近已经开发出一些方法，这些方法允许在适当的细胞因子条件下，从某些组织（包括人外周血）中提取出类似LC的树突状细胞（DC），从而在培养物中进行扩增。研究表明，人类血液来源的类LC细胞与选定的强力接触性过敏原（例如2,4-二硝基氟苯（DNFB））一起刺激选择性的表型变化，包括白介素1β（IL-1β）的上调在皮肤刺激物无效的条件下，mRNA表达。但是，在我们自己以前的研究中，我们发现献血者之间在DC对DNFB诱导的IL-1β表达变化的反应性方面似乎存在差异，这些差异可能会损害该方法作为一种实用性。接触性过敏原的筛选方法。因此，我们研究了供体对一组已知的人类接触性过敏原（DNFB;对苯二胺，PPD;甲基-氯异噻唑啉酮/甲基异噻唑啉酮，CMIT），皮肤刺激性苯扎氯铵和有丝分裂佛波醇肉豆蔻酸酯乙酸盐（DCA）的DC反应性的变异性。 。来自所有供体的树突状细胞组成性表达IL-1βmRNA。用PPD或CMIT处理从对DNFB有反应性表型的供体分离的DC也会导致IL-1βmRNA表达上调，尽管这种变化总是比较适度，与媒介物对照相比，通常导致诱导两倍。在有丝分裂原PMA引起的IL-1β表达增加与对过敏原反应的捐助者观察到的相似的增加的条件下，源自对DNFB无反应型的捐助者的树突状细胞也无法对这些额外的接触过敏原做出反应。苯扎氯铵在任何接受检查的供体中均不能引起这种细胞因子表达的改变，而不论其应答者表型如何。证实了应答者/非应答者DC表型的时间稳定性，并且在约18个月的时间内观察到了关于DNFB诱导的IL-1βmRNA表达变化的稳定表型。在此期间测试的捐献者中有百分之五十（6/12）表现出反应者表型。这些数据表明化学过敏原确实刺激了具有反应性表型的供体比例中IL-1βmRNA表达的一致变化，并且使用迄今评估的相对较窄范围的材料，此类反应显然对过敏原具有选择性。然而，对非常强的接触性过敏原的适度反应，加上反应者/非反应者表型的困难，意味着以目前的形式，这种方法不能用于皮肤敏化活性的常规评估。版权所有2001 John Wiley＆Sons，Ltd.

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