Enk A H, Katz S I
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1398-402. doi: 10.1073/pnas.89.4.1398.
To assess changes in epidermis-derived cytokine mRNA levels early in the afferent phase of allergic contact sensitivity, total epidermal mRNA was analyzed at various times after painting skin with haptens. We used a sensitive reverse transcriptase-polymerase chain reaction technique to quantitatively compare the regulation patterns of the following mRNAs: class II major histocompatibility complex I-A alpha, tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1 alpha, IL-1 beta, interferon (IFN) gamma, granulocyte/macrophage colony-stimulating factor, IFN-induced protein 10, and macrophage inflammatory protein 2. Enhanced Langerhans cell-derived IL-1 beta mRNA signals were detected as early as 15 min after skin painting with allergens. TNF-alpha, IFN-gamma, and granulocyte/macrophage colony-stimulating factor mRNAs were found to be upregulated after application of allergens, irritant, and tolerogens, but class II major histocompatibility complex I-A alpha, IL-1 alpha, IL-1 beta, IFN-induced protein 10, and macrophage inflammatory protein 2 mRNAs were upregulated only after allergen painting. Depletion of specific cell populations demonstrated that Langerhans cells were the primary source of the IL-1 beta and class II major histocompatibility complex I-A alpha mRNAs, keratinocytes were the primary source of TNF-alpha, IL-1 alpha, IFN-induced protein 10, and macrophage inflammatory protein 2, and infiltrating T lymphocytes were the source of IFN-gamma. Relevance of the molecular findings was demonstrated by the identification of biologically active IL-1 alpha and immunoreactive TNF-alpha in culture supernatants. These studies demonstrate that Langerhans cell-derived and certain keratinocyte-derived cytokine mRNAs are selectively upregulated by allergens in the very early afferent phase of contact sensitivity.
为了评估过敏性接触性皮炎传入期早期表皮来源细胞因子mRNA水平的变化，在用半抗原涂抹皮肤后的不同时间对全层表皮mRNA进行分析。我们使用敏感的逆转录聚合酶链反应技术定量比较以下mRNA的调控模式：II类主要组织相容性复合体I-Aα、肿瘤坏死因子α（TNF-α）、白细胞介素（IL）1α、IL-1β、干扰素（IFN）γ、粒细胞/巨噬细胞集落刺激因子、IFN诱导蛋白10和巨噬细胞炎性蛋白2。在用变应原涂抹皮肤后15分钟，最早检测到朗格汉斯细胞来源的IL-1β mRNA信号增强。发现TNF-α、IFN-γ和粒细胞/巨噬细胞集落刺激因子mRNA在用变应原、刺激物和耐受原处理后上调，但II类主要组织相容性复合体I-Aα、IL-1α、IL-1β、IFN诱导蛋白10和巨噬细胞炎性蛋白2 mRNA仅在变应原涂抹后上调。特定细胞群的清除表明，朗格汉斯细胞是IL-1β和II类主要组织相容性复合体I-Aα mRNA的主要来源，角质形成细胞是TNF-α、IL-1α、IFN诱导蛋白10和巨噬细胞炎性蛋白2的主要来源，浸润的T淋巴细胞是IFN-γ的来源。培养上清液中生物活性IL-1α和免疫反应性TNF-α的鉴定证明了分子研究结果的相关性。这些研究表明，在接触性皮炎非常早期的传入期，变应原选择性上调朗格汉斯细胞来源和某些角质形成细胞来源的细胞因子mRNA。
