Marvin K W, Hansen W R, Miller H C, Eykholt R L, Mitchell M D
Department of Pharmacology and Clinical Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand.
J Mol Endocrinol. 1999 Apr;22(2):193-205. doi: 10.1677/jme.0.0220193.
We have examined the expression of the intercellular adhesion molecule-1 (ICAM-1) mRNA in primary and established amnion-derived cell cultures and regulation of this expression by tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta. TNF-alpha (50 ng/ml) and IL-1beta (1.0 ng/ml) induced 18- and 11-fold increases respectively in expression of the ICAM-1 mRNA in WISH cells (an amnion epithelium-derived cell line). The increase was detectable within one hour of treatment and peaked by two hours. The protein synthesis inhibitor, cycloheximide (10 microg/ml) did not inhibit this induction. Increased levels of ICAM-1 protein were detected in the cells within 4 h after initiation of treatment with either cytokine. By 16 h of treatment with IL-1beta or TNF-alpha ICAM-1 reached 40 and 73 pg/microg cellular protein, representing 6- and 11-fold stimulations respectively. In primary amnion cells, basal expression of ICAM-1 mRNA was undetectable. However, TNF-alpha (50 ng/ml) induced ICAM-1 mRNA within two hours, peak expression being reached between four and eight hours after initiation of treatment. The present report demonstrates for the first time that amnion derived cells can express ICAM-1 and, further, that this expression is regulated by pro-inflammatory cytokines. This has implications for the amnion as a possible source for soluble ICAM-1, for this gene product as a marker for preterm labour, and for participation of the amnion, additional to its reported secretory role, in inflammatory processes of the fetal membranes.
我们检测了原代和已建立的羊膜来源细胞培养物中细胞间黏附分子-1（ICAM-1）mRNA的表达，以及肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-1β对该表达的调节。TNF-α（50 ng/ml）和IL-1β（1.0 ng/ml）分别使WISH细胞（一种羊膜上皮来源的细胞系）中ICAM-1 mRNA的表达增加了18倍和11倍。在处理后1小时内即可检测到这种增加，并在2小时达到峰值。蛋白质合成抑制剂环己酰亚胺（10 μg/ml）并未抑制这种诱导作用。在用任何一种细胞因子处理后4小时内，细胞中检测到ICAM-1蛋白水平升高。在用IL-1β或TNF-α处理16小时后，ICAM-1分别达到40和73 pg/μg细胞蛋白，分别代表6倍和11倍的刺激。在原代羊膜细胞中，未检测到ICAM-1 mRNA的基础表达。然而，TNF-α（50 ng/ml）在两小时内诱导了ICAM-1 mRNA的表达，在处理开始后4至8小时达到峰值表达。本报告首次证明羊膜来源的细胞可以表达ICAM-1，并且进一步表明这种表达受促炎细胞因子调节。这对于羊膜作为可溶性ICAM-1的可能来源、该基因产物作为早产标志物以及羊膜除了其已报道的分泌作用外还参与胎膜炎症过程具有重要意义。
