Weinberger M S, Davidson T M, Broide D H
Division of Head and Neck Surgery, University of California, San Diego 92093-0635, USA.
J Allergy Clin Immunol. 1996 Feb;97(2):662-71. doi: 10.1016/s0091-6749(96)70312-3.
IL-1 and tumor necrosis factor (TNF) are cytokines that share many overlapping functions, including induction of expression of the vascular cell adhesion molecule (VCAM) by endothelial cells. However, because most studies of cytokine induction of adhesion molecules have used human umbilical vein endothelial cells (HUVECs) and not microvascular endothelial cells, the functional significance of such observations to sites of allergic inflammation, such as the nasal mucosa, are at present unknown. We have therefore used nasal mucosa to compare the functional response of these microvascular endothelial cells with HUVECs. HUVECs or nasal mucosal explants were stimulated in vitro with varying concentrations of IL-1 or TNF for 0 to 48 hours, and VCAM mRNA and protein expression were determined by means of immunostaining and in situ hybridization. TNF and IL-1 were equivalent in their ability to induce VCAM mRNA and protein expression by HUVECs. In contrast, TNF was significantly more potent than IL-1 in inducing VCAM mRNA and protein expression by nasal mucosal microvascular endothelial cells. The recovery of significant amounts of IL-1 after incubation of recombinant IL-1 with nasal mucosa, as well as the ability of IL-1 to induce intercellular adhesion molecular expression by nasal mucosa, suggests that neither degradation of IL-1 nor downregulation of IL-1 receptors in nasal mucosa is likely to explain the inability of IL-1 to induce VCAM expression by nasal mucosa. These studies suggest that microvascular endothelial cells in the nasal mucosa differ functionally from HUVECs and that TNF may be more important than IL-1 in induction of VCAM expression in the nasal mucosa.
白细胞介素-1（IL-1）和肿瘤坏死因子（TNF）是具有许多重叠功能的细胞因子，包括诱导内皮细胞表达血管细胞黏附分子（VCAM）。然而，由于大多数关于细胞因子诱导黏附分子的研究使用的是人脐静脉内皮细胞（HUVECs）而非微血管内皮细胞，目前尚不清楚此类观察结果对过敏性炎症部位（如鼻黏膜）的功能意义。因此，我们利用鼻黏膜来比较这些微血管内皮细胞与HUVECs的功能反应。将HUVECs或鼻黏膜外植体在体外用不同浓度的IL-1或TNF刺激0至48小时，通过免疫染色和原位杂交测定VCAM mRNA和蛋白表达。TNF和IL-1在诱导HUVECs表达VCAM mRNA和蛋白方面能力相当。相比之下，TNF在诱导鼻黏膜微血管内皮细胞表达VCAM mRNA和蛋白方面比IL-1显著更有效。重组IL-1与鼻黏膜孵育后回收了大量IL-1，以及IL-1诱导鼻黏膜表达细胞间黏附分子的能力，这表明IL-1的降解或鼻黏膜中IL-1受体的下调都不太可能解释IL-1无法诱导鼻黏膜表达VCAM的原因。这些研究表明，鼻黏膜中的微血管内皮细胞在功能上与HUVECs不同，并且TNF在诱导鼻黏膜VCAM表达方面可能比IL-1更重要。
