The chemokine repertoire of human dermal microvascular endothelial cells and its regulation by inflammatory cytokines
The chemokine repertoire of human dermal microvascular endothelial cells and its regulation by inflammatory cytokines
复制标题
DOI：
10.1111/1523-1747.ep12289711
复制
发表时间：
1997-04-01
影响因子：
6.5
通讯作者：
Gillitzer, R
中科院分区：
文献类型：
--
作者：
Goebeler, M;Yoshimura, T;Gillitzer, R
内皮细胞的激活是炎症过程启动过程中的一个关键事件，与细胞粘附分子和细胞因子的诱导有关。细胞因子包括趋化活性细胞因子（趋化因子），可促进白细胞从循环到炎症发展部位的渗出。在本研究中，我们评估了源自皮肤的人内皮细胞（HDMEC）的趋化因子库，以及细胞因子、HDMEC 和细胞因子对这些趋化因子的调节。研究永生化人真皮微血管内皮细胞系 HMEC-1 在 mRNA 和蛋白质水平上的 C-X-C 和 C-C 趋化因子表达。在用白细胞介素 1 β (IL-1 β) 和肿瘤坏死因子 α (TNF-α) 刺激后，HDMEC 和 HMEC-1 均表达高水平的 ILS、GRO 和单核细胞趋化蛋白 1 (MCP-I)，RANTES仅被微弱诱导；然而，TNF-α和干扰素-γ（IFN-γ）同时治疗导致RANTES上调，表明这两种细胞因子之间存在协同作用。C-X-C趋化因子IFN诱导蛋白-11被IFN-γ上调，但不被研究的其他细胞因子上调，巨噬细胞炎症蛋白1α和β、I-309和ENA-78不能被诱导。将 HDMEC 和 HMEC-1 的趋化因子库与湖南脐静脉内皮的趋化因子库进行比较，发现其非常相似，但重要的例外是 IFN-γ 和 IL-4 仅在大血管内皮中上调 MCP-1。我们的数据表明，HDMEC 通过选择性产生 MCP-1、IL-8、GRO、RANTES 和 IP-10 来促进真皮细胞因子网络，这可能会严重影响白细胞亚群的位点特异性募集。
Activation of endothelium is a critical event during the initiation of inflammatory processes and is associated with the induction of cell adhesion molecules and cytokines, The latter include chemotactically active cytokines (chemokines) that promote leukocyte diapedesis from the circulation to sites of evolving inflammation, In this study we evaluated the chemokine repertoire of human endothelial cells derived from the skin (HDMECs) and regulation of these chemokines by cytokines, HDMECs and an immortalized human dermal microvascular endothelial cell line, HMEC-1, were investigated for the expression of C-X-C and C-C chemokines at mRNA and protein levels, Upon stimulation with interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), both HDMECs and HMEC-1 expressed high levels of ILS, GRO, and monocyte chemoattractant protein-1 (MCP-I), RANTES was only weakly induced; however, concomitant treatment with TNF-alpha and interferon-gamma (IFN-gamma) led to upregulation of RANTES, indicating a synergy between these two cytokines, The C-X-C chemokine IFN-inducible protein-ill was upregulated by IFN-gamma but not by other cytokines studied, Macrophage inflammatory protein-1 alpha and beta, I-309, and ENA-78 could not be induced. The chemokine repertoires of HDMECs and HMEC-1 were compared to those of hunan umbilical vein endothelium and found to be rather similar with the important exception that IFN-gamma and IL-4 up-regulated MCP-1 only in macrovascular endothelium. Our data indicate that HDMECs contribute to the dermal cytokine network by selective production of MCP-1, IL-8, GRO, RANTES, and IP-10, which may critically influence the site-specific recruitment of leukocyte subsets.