Myometrial Tumor Necrosis Factor-α Receptors Increase With Gestation and Labor and Modulate Gene Expression Through Mitogen-Activated Kinase and Nuclear Factor-κB
Myometrial Tumor Necrosis Factor-α Receptors Increase With Gestation and Labor and Modulate Gene Expression Through Mitogen-Activated Kinase and Nuclear Factor-κB
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DOI：
10.1177/1933719111413297
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发表时间：
2012-01-01
影响因子：
2.9
通讯作者：
Johnson, Mark R.
中科院分区：
文献类型：
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作者：
Alexander, Helen A.;Sooranna, Suren R.;Johnson, Mark R.
以前，我们发现子宫肌层肿瘤坏死因子-α（TNF-α）信使RNA（mRNA）的表达并没有随着早产或足月分娩而增加。为了进一步研究TNF-α在人类分娩中的作用，我们研究了TNF-α受体（TNFR1A和B）的表达，调节，以及相关的细胞内信号通路，在人类子宫肌层样本中获得之前和之后的劳动和子宫平滑肌细胞（USMCs）的原代培养。我们发现，这两种受体的mRNA表达增加，随着妊娠和劳动和TNFR1B蛋白水平的进展，在长期劳动子宫肌层样品显着高于nonlabour控制。肿瘤坏死因子-α：USMCs的处理激活了所有促分裂原活化蛋白激酶（MAPK）亚型和核因子κ-B（NF-κ B）。TNF-α诱导的TNFR 1 B和前列腺素H合酶2型表达的增加分别被NF-κ B和MAPK抑制剂降低。TNF-α诱导的白细胞介素8（IL-8）的增加似乎不依赖于MAPK和NF-κ B通路。这些数据表明，随着妊娠和分娩的推进，子宫可能对TNF-α的作用变得更加敏感，并且TNF-α通过MAPK和NF-κ B起作用以促进分娩相关基因的表达。
Previously, we found that myometrial tumor necrosis factor-alpha (TNF-alpha) messenger RNA (mRNA) expression did not increase with preterm or term labor. To further investigate the role of TNF-alpha in human labor, we studied TNF-alpha receptor (TNFR1A and B) expression, regulation, and associated intracellular signaling pathways in human myometrial samples obtained both before and after the onset of labor and in primary cultures of uterine smooth muscle cells (USMCs). We found that the mRNA expression of both receptors increased with advancing gestation and labor and protein levels of TNFR1B were significantly higher in term laboring myometrial samples than in nonlabor controls. Tumor necrosis factor-alpha: treatment of USMCs activated all mitogen-activated protein kinase (MAPK) subtypes and nuclear factor kappa-B (NF-kappa B). The TNF-alpha induced increases in the expression of TNFR1B and prostaglandin H synthase type 2 were reduced by inhibitors of NF-kappa B and MAPKs, respectively. The TNF-alpha induced increase in interleukin 8 (IL-8) appeared to be independent of MAPK and NF-kappa B pathway. These data suggest that the uterus may become more sensitive to the action of TNF-alpha with advancing gestation and labor and that TNF-alpha acts via MAPK and NF-kappa B to promote labor-associated gene expression.