Caughman S W, Li L J, Degitz K
Department of Dermatology, Veteran Affairs Medical Center, Atlanta, Georgia.
J Invest Dermatol. 1992 Jun;98(6 Suppl):61S-65S. doi: 10.1111/1523-1747.ep12462226.
Cell adhesion molecules are cell-surface proteins that allow specific cell-cell interactions among leukocytes, as well as between leukocytes and other cells. Recent studies have shown that the differential expression of selected cell-adhesion molecules plays a critical role in cutaneous inflammation, immunologic responses, and wound repair. Intercellular adhesion molecule-1 (ICAM-1) is a cell-adhesion molecule that is constitutively expressed on human dermal microvascular endothelial cells (HDMEC) and is inducible on human keratinocytes (HK). Its regulated expression is vital to the initiation and evolution of localized inflammatory processes in the skin. ICAM-1 serves as a specific ligand for lymphocyte function-associated antigen-1 (LFA-1), a cell-surface protein expressed on all leukocytes. The regulated expression of ICAM-1 allows leukocytes to bind to endothelial cells at sites of inflammation and, after exiting into the tissue, to interact with specific target cells, such as HK. Furthermore, specific cytokines are capable of differentially regulating ICAM-1 expression on HDMEC, HK, and other cells. The biologic relevance of ICAM-1 expression in cutaneous inflammation is further supported by functional studies demonstrating the critical role of ICAM-1/LFA-1 interactions in mediating the binding of peripheral blood leukocytes to HDMEC and to HK--cells known to be participants and targets in specific cutaneous immunologic responses. Thus, the delineation of precise molecular mechanisms that regulate the tissue-specific and cytokine-specific expression if ICAM-1 is important to both our understanding of the biology of localized inflammation and to the development of directed anti-inflammatory therapeutic strategies. Current evidence indicates that ICAM-1 expression is regulated at the level of gene transcription. Recently our laboratory has isolated and characterized a human genomic clone that contains the 5' regulatory region of the ICAM-1 gene. In the current studies, we further describe the genomic ICAM-1 clones isolated to date and demonstrate the presence of consensus regulatory elements located within the 5' flanking region of the ICAM-1 gene that are potentially involved in regulating ICAM-1 gene transcription.
细胞黏附分子是一类细胞表面蛋白，可使白细胞之间以及白细胞与其他细胞之间发生特定的细胞间相互作用。最近的研究表明，特定细胞黏附分子的差异表达在皮肤炎症、免疫反应和伤口修复中起关键作用。细胞间黏附分子-1（ICAM-1）是一种细胞黏附分子，在人真皮微血管内皮细胞（HDMEC）上组成性表达，在人角质形成细胞（HK）上可诱导表达。其表达的调控对皮肤局部炎症过程的起始和演变至关重要。ICAM-1作为淋巴细胞功能相关抗原-1（LFA-1）的特异性配体，LFA-1是一种在所有白细胞上表达的细胞表面蛋白。ICAM-1表达的调控使白细胞能够在炎症部位与内皮细胞结合，并在进入组织后与特定靶细胞（如HK）相互作用。此外，特定细胞因子能够差异调节HDMEC、HK和其他细胞上ICAM-1的表达。功能研究表明ICAM-1/LFA-1相互作用在介导外周血白细胞与HDMEC以及与HK（已知是特定皮肤免疫反应的参与者和靶细胞）的结合中起关键作用，这进一步支持了ICAM-1表达在皮肤炎症中的生物学相关性。因此，阐明调节ICAM-1组织特异性和细胞因子特异性表达的精确分子机制，对于我们理解局部炎症生物学以及开发定向抗炎治疗策略都很重要。目前的证据表明，ICAM-1的表达在基因转录水平受到调控。最近我们实验室分离并鉴定了一个包含ICAM-1基因5'调控区的人类基因组克隆。在当前研究中，我们进一步描述了迄今为止分离的基因组ICAM-1克隆，并证明在ICAM-1基因5'侧翼区域存在潜在参与调节ICAM-1基因转录的共有调控元件。
