Department of Forensic Medicine, Wakayama Medical University, Wakayama, Japan.
Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.
PLoS One. 2018 Nov 6;13(11):e0207085. doi: 10.1371/journal.pone.0207085. eCollection 2018.
Preterm labor (PTL) is the most common cause of neonatal death and long-term adverse outcome. The pharmacological agents for PTL prevention are palliative and frequently fail to prevent PTL and improve neonatal outcome. It is essential to fully understand the molecular mechanisms of PTL in order to develop novel therapeutic methods against PTL. Several lines of evidence indicate some chemokines are expressed in gestational tissues during labor or PTL. To reveal the pathophysiological roles of the CX3CL1-CX3CR1 axis in PTL, we performed present study using LPS-induced PTL mice model in CX3CR1-deficient (Cx3cr1-/-) mice. We indicated that PTL was suppressed in Cx3cr1-/- mice and immunoneutralization of CX3CL1 in WT mice. From immunohistochemical and the gene expression analyses, the CX3CL1-CX3CR1 axis has detrimental roles in PTL through intrauterine recruitment of macrophages and the enhancement of macrophage-derived inflammatory mediators. Thus, the CX3CL1-CX3CR1 axis may be a good molecular target for preventing PTL.
早产（PTL）是新生儿死亡和长期不良结局的最常见原因。PTL 预防的药物治疗是姑息性的，并且经常不能预防 PTL 和改善新生儿结局。为了开发针对 PTL 的新治疗方法，全面了解 PTL 的分子机制至关重要。有几条证据表明，一些趋化因子在分娩或 PTL 期间在妊娠组织中表达。为了揭示 CX3CL1-CX3CR1 轴在 PTL 中的病理生理作用，我们使用 LPS 诱导的 PTL 小鼠模型在 CX3CR1 缺陷（Cx3cr1-/-）小鼠中进行了本研究。我们表明，PTL 在 Cx3cr1-/- 小鼠中受到抑制，并且在 WT 小鼠中免疫中和 CX3CL1。从免疫组织化学和基因表达分析来看，CX3CL1-CX3CR1 轴通过宫内招募巨噬细胞和增强巨噬细胞衍生的炎症介质在 PTL 中发挥有害作用。因此，CX3CL1-CX3CR1 轴可能是预防 PTL 的一个很好的分子靶点。
