IL-18-induced expression of intercellular adhesion molecule-1 in human monocytes: involvement in IL-12 and IFN-gamma production in PBMC.
IL-18-induced expression of intercellular adhesion molecule-1 in human monocytes: involvement in IL-12 and IFN-gamma production in PBMC.
复制标题
IL-18 诱导人单核细胞中细胞间粘附分子 1 的表达：参与 PBMC 中 IL-12 和 IFN-γ 的产生。
作者：
A. Yoshida;H. Takahashi;M. Nishibori;H. Iwagaki;T. Yoshino;T. Morichika;M. Yokoyama;E. Kondo;T. Akagi;N. Tanaka
流式细胞仪分析表明，IL-18呈时间和浓度依赖性地上调人PBMC单核细胞群细胞间黏附分子-1(ICAM-1)的表达，而单核细胞CD11a、CD18、CD29、CD44和CD62L的表达以及T细胞ICAM-1、CD11a、CD18、CD29、CD44和CD62L的表达不受IL-18影响。IL-18在相同浓度范围内可刺激PBMC产生IL-12、TNF-α和干扰素-γ，但IL-18诱导的单核细胞ICAM-1的表达不受抗IL-12、抗TNF-α和抗干扰素-γ抗体的抑制，提示IL-18对内源性IL-12、TNF-α和干扰素-γ产生的上调作用是独立的。IL-18还可诱导PBMC聚集，抗ICAM-1和抗LFA-1单抗可阻断IL-18诱导的PBMC聚集。另一方面，抗ICAM-1和抗LFA-1单抗对IL-18诱导的IL-12、干扰素-γ和肿瘤坏死因子-α三种细胞因子的产生分别抑制60%和40%。这些结果有力地表明，IL-18诱导的ICAM-1的上调以及随后通过单核细胞上的ICAM-1和T/NK细胞上的LFA-1的黏附相互作用，为IL-18启动的细胞因子级联反应产生了额外的刺激信号和有效的旁分泌环境。
IL-18 time- and concentration-dependently upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) in a monocyte population in human PBMC as determined by FACS analysis while the expression of CD11a, CD18, CD29, CD44, and CD62L in monocytes and that of ICAM-1, CD11a, CD18, CD29, CD44, and CD62L in T cells was not influenced by IL-18. IL-18 in the same concentration range stimulated the production of IL-12, TNF-alpha, and IFN-gamma in culture of PBMC; however, IL-18-induced expression of ICAM-1 in monocytes was not inhibited by anti-IL-12, anti-TNF-alpha, or anti-IFN-gamma Ab, suggesting the independence of the upregulating effect of IL-18 on endogenous IL-12, TNF-alpha, and IFN-gamma production. IL-18 also induced the aggregation of PBMC, which was prevented by anti-ICAM-1 and anti-LFA-1 Abs. On the other hand, anti-ICAM-1 and anti-LFA-1 Abs inhibited IL-18-induced production of three cytokines, IL-12, IFN-gamma, and TNF-alpha, by 60 and 40%, respectively. These results strongly suggested that the IL-18-induced upregulation of ICAM-1 and the subsequent adhesive interaction through ICAM-1 on monocytes and LFA-1 on T/NK cells generate an additional stimulatory signaling as well as an efficient paracrine environment for the IL-18-initiated cytokine cascade.