Kashihara-Sawami M, Norris D A
Department of Dermatology, University of Colorado School of Medicine, Denver 80262.
J Invest Dermatol. 1992 May;98(5):741-7. doi: 10.1111/1523-1747.ep12499938.
Inducing the expression of ICAM-1 (CD54) on the surface of epidermal keratinocytes is an important step in initiating leukocyte interaction with the epidermis. We studied the effect of keratinocyte differentiation and of drugs used to treat epidermal inflammation on the induction of this important adhesion molecule. Cell membrane expression of ICAM-1 in cultured human keratinocytes was analyzed using both immunofluorescence and FACS analysis of staining with anti-ICAM-1 monoclonal antibody and was correlated with markers of keratinocyte differentiation. Cell-surface ICAM-1 expression was induced by gamma interferon in all culture conditions, but was significantly greater (p less than 0.014) in cells grown in low-calcium medium ([Ca++] 0.03 mM), and correlated with increased staining for the basal cell keratin K5. The synthetic retinoid Etretin (Ro 10-1670) enhanced the interferon-induced ICAM-1 expression over a wide concentration range (10(-8)-10(-5) M); however, this effect was only seen in the more differentiated cells grown in 0.15 mM and 1.0 mM calcium and not in the cells grown in 0.03 mM calcium. The Etretin effects on intracellular K5 staining paralleled those on cell-surface ICAM-1. Anti-inflammatory glucocorticoids had no effect on ICAM-1 expression in cultured human keratinocytes, even at suboptimal gamma interferon doses (5 U/ml). beta-estradiol, on the other hand, mimicked the Etretin effect, increasing both IFN induction of ICAM-1 expression and K5 staining in more differentiated keratinocytes in 0.15 and 1.0 mM calcium, but not in those in 0.03 mM calcium. Both Etretin and beta-estradiol decreased staining of involucrin, a marker of terminal differentiation, supporting the proposition that in this experimental system these drugs suppress keratinocyte differentiation. The enhanced ICAM-1 induction in keratinocytes with a basal level of differentiation correlates with the in vivo effects of interferon on ICAM-1 and may be a principal determinant in the patterns of ICAM-1 seen in inflammatory skin diseases.
诱导表皮角质形成细胞表面ICAM-1（CD54）的表达是启动白细胞与表皮相互作用的重要步骤。我们研究了角质形成细胞分化以及用于治疗表皮炎症的药物对这种重要黏附分子诱导的影响。使用抗ICAM-1单克隆抗体染色的免疫荧光和FACS分析来检测培养的人角质形成细胞中ICAM-1的细胞膜表达，并将其与角质形成细胞分化的标志物相关联。在所有培养条件下，γ干扰素均可诱导细胞表面ICAM-1的表达，但在低钙培养基（[Ca++] 0.03 mM）中生长的细胞中，其表达显著更高（p小于0.014），并且与基底细胞角蛋白K5的染色增加相关。合成维甲酸依曲替酯（Ro 10-1670）在较宽的浓度范围（10(-8)-10(-5) M）内增强了干扰素诱导的ICAM-1表达；然而，这种作用仅在生长于0.15 mM和1.0 mM钙中的分化程度较高的细胞中观察到，而在生长于0.03 mM钙中的细胞中未观察到。依曲替酯对细胞内K5染色的影响与对细胞表面ICAM-1的影响相似。抗炎糖皮质激素对培养的人角质形成细胞中的ICAM-1表达没有影响，即使在次优γ干扰素剂量（5 U/ml）下也是如此。另一方面，β-雌二醇模拟了依曲替酯的作用，在0.15 mM和1.0 mM钙中生长的分化程度较高的角质形成细胞中，增加了ICAM-1表达的IFN诱导以及K5染色，但在0.03 mM钙中的细胞中未增加。依曲替酯和β-雌二醇均降低了终末分化标志物兜甲蛋白的染色，支持了在该实验系统中这些药物抑制角质形成细胞分化的观点。在具有基础分化水平的角质形成细胞中增强的ICAM-1诱导与干扰素对ICAM-1的体内作用相关，并且可能是炎症性皮肤病中所见ICAM-1模式的主要决定因素。
