Imperial College Parturition Research Group, Academic Department of Obstetrics & Gynaecology, Imperial College School of Medicine Chelsea and Westminster Hospital, London, UK.
Reprod Sci. 2012 Jan;19(1):43-54. doi: 10.1177/1933719111413297.
Previously, we found that myometrial tumor necrosis factor-α (TNF-α) messenger RNA (mRNA) expression did not increase with preterm or term labor. To further investigate the role of TNF-α in human labor, we studied TNF-α 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- treatment of USMCs activated all mitogen-activated protein kinase (MAPK) subtypes and nuclear factor κ-B (NF-κB). The TNF-α induced increases in the expression of TNFR1B and prostaglandin H synthase type 2 were reduced by inhibitors of NF-κB and MAPKs, respectively. The TNF-α induced increase in interleukin 8 (IL-8) appeared to be independent of MAPK and NF-κB pathway. These data suggest that the uterus may become more sensitive to the action of TNF-α with advancing gestation and labor and that TNF-α acts via MAPK and NF-κB to promote labor-associated gene expression.
此前，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产而增加。为了进一步研究 TNF-α 在人类分娩中的作用，我们研究了在分娩开始前后及在子宫平滑肌细胞（USMC）原代培养物中获得的人子宫肌样本中 TNF-α 受体（TNFR1A 和 B）的表达、调节和相关细胞内信号通路。我们发现，两种受体的 mRNA 表达随着妊娠和分娩的进展而增加，并且在足月产的子宫肌样本中 TNFR1B 的蛋白水平明显高于非分娩对照组。肿瘤坏死因子-α处理 USMC 可激活所有丝裂原激活蛋白激酶（MAPK）亚型和核因子 κ-B（NF-κB）。NF-κB 和 MAPKs 的抑制剂分别降低了 TNF-α诱导的 TNFR1B 和前列腺素 H 合酶 2 的表达增加。TNF-α 诱导的白细胞介素 8（IL-8）的增加似乎独立于 MAPK 和 NF-κB 途径。这些数据表明，随着妊娠和分娩的进展，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-κB 促进与分娩相关的基因表达。
