Identification of interleukin-1β regulated genes in uterine smooth muscle cells
Identification of interleukin-1β regulated genes in uterine smooth muscle cells
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DOI：
10.1530/rep-07-0289
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发表时间：
2007-12-01
期刊：
影响因子：
3.8
通讯作者：
Blank, Volker
中科院分区：
文献类型：
--
作者：
Chevillard, Gregory;Derjuga, Anna;Blank, Volker
我们分析了子宫平滑肌细胞对白细胞介素-1 β（IL-1 β）的反应。我们首先发现，PHM 1 -31子宫肌层细胞，我们的细胞模型，是收缩的。为了确定促炎细胞因子激活子宫平滑肌细胞的分子机制，我们在IL-1 β存在和不存在的情况下对PHM 1 -31细胞进行了基因芯片表达谱研究。总之，我们鉴定了198个已知基因，其mRNA水平在IL-1 β暴露后显著调节（>2.0倍变化）。我们通过独立的mRNA和蛋白质分析证实了所选基因的表达变化。由IL-1 β诱导的基因组包括转录因子和炎症反应基因，例如B细胞中κ轻链多肽基因增强子的核因子（NF κ B）、五聚体相关基因（PTX 3）和肿瘤坏死因子α诱导蛋白3/A20（TNFAIP 3/A20）。我们还发现趋化因子如C-X-C基序配体3（CXCL 3）和细胞外基质重塑信号分子如腱生蛋白C（TNC）的上调。我们的数据表明，IL-1 β促进了细胞基因网络的快速激活，特别是与炎症反应有关的基因网络，这可能会产生有利于子宫肌层细胞收缩的细胞环境。我们的研究结果提供了新的见解子宫平滑肌细胞的调节机制，并可能感染诱导早产。
We analyzed the response of uterine smooth muscle cells to interleukin-1 beta (IL-1 beta). We first showed that PHM1-31 myometrial cells, our cellular model, are contractile. To determine the molecular mechanisms of uterine smooth muscle cell activation by proinflarnmatory cytokines, we performed genechip expression array profiling studies of PHM1-31 cells in the absence and the presence of IL-1 beta. In total, we identified 198 known genes whose mRNA levels are significantly modulated (>2.0-fold change) following IL-1 beta exposure. We confirmed the expression changes for selected genes by independent mRNA and protein analysis. The group of genes induced by IL-1 beta includes transcription factors and inflammatory response genes such as nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF kappa B), pentraxin-related gene (PTX3), and tumor necrosis factor alpha-induced protein 3/A20 (TNFAIP3/A20). We also found up-regulation of chemokines like C-X-C motif ligand 3 (CXCL3) and extracellular matrix remodeling signaling molecules like tenascin C (TNC). Our data suggest that IL-1 beta elicits the rapid activation of a cellular network of genes particularly implicated in inflammatory response that may create a cellular environment favorable for myometrial cell contraction. Our results provide novel insights into the mechanisms of uterine smooth muscle cell regulation and possibly infection-induced preterm labor.