Fouladi-Nashta A A, Mohamet L, Heath J K, Kimber S J
Faculty of Life Sciences, The University of Manchester, Core Technology Facility, Manchester M13 9MNT, United Kingdom.
Biol Reprod. 2008 Jul;79(1):142-53. doi: 10.1095/biolreprod.107.065219. Epub 2008 Mar 12.
This study addresses the regulation of the interleukin 1 (IL1) system in the murine uterine luminal epithelium (LE) and stroma by leukemia inhibitory factor (LIF). Using RT-PCR we compared expression of Il1a, Il1b, Il1rn, Il1r1, and Il1r2 during the pre- and peri-implantation periods of pregnancy in wild-type (WT) and LIF-null LE and stroma. In WT LE, Il1a transcripts were down-regulated on Day 4 of pregnancy (D4), with renewed expression by the evening of D4 (D4 pm). In Lif(-/-) LE there was a gradual decrease in expression on D2, and expression became undetectable by D6. Il1b and Il1r1 expression were similar in WT and null mice, but Il1rn expression was almost completely lost during the peri-implantation period in Lif(-/-) LE. In the stroma, Il1a was sharply down-regulated on D4 and reappeared on D4 pm but was only expressed from D3 to D5 in the null mice. Stromal Il1r1 and Il1r2 were also misregulated. Il1rn showed constitutive expression in null stroma in contrast to the loss of expression on D4 in the WT mouse. In Lif-deficient mice, immunostaining indicated a reduction of endometrial IL1A at the time of implantation and of IL1B in stroma. LE-stromal coculture revealed that LIF stimulated the apical secretion of both IL1A and PTGES2 by LE cells without affecting basal secretion of IL1A and with only a small effect on basal PTGES2 secretion. We conclude that Il1a and Il1rn in LE and Il1a, Il1rn, and Il1r1 in stroma are regulated by LIF, which stimulates apical secretion of IL1A by LE.
本研究探讨白血病抑制因子（LIF）对小鼠子宫腔上皮（LE）和基质中白细胞介素1（IL1）系统的调节作用。我们利用逆转录聚合酶链反应（RT-PCR）比较了野生型（WT）和LIF基因敲除小鼠的LE和基质在妊娠前及着床期Il1a、Il1b、Il1rn、Il1r1和Il1r2的表达情况。在WT小鼠的LE中，妊娠第4天（D4）Il1a转录本下调，而在D4傍晚（D4 pm）重新表达。在Lif(-/-)小鼠的LE中，D2时表达逐渐降低，到D6时表达无法检测到。WT和基因敲除小鼠中Il1b和Il1r1的表达相似，但在Lif(-/-)小鼠的LE着床期，Il1rn表达几乎完全丧失。在基质中，WT小鼠D4时Il1a急剧下调，D4 pm重新出现，但在基因敲除小鼠中仅在D3至D5表达。基质中的Il1r1和Il1r2也存在调节异常。与WT小鼠D4时表达缺失相反，Il1rn在基因敲除小鼠的基质中呈组成性表达。在LIF缺陷小鼠中，免疫染色显示着床时子宫内膜IL1A减少，基质中IL1B减少。LE-基质共培养显示，LIF刺激LE细胞顶端分泌IL1A和PTGES2，而不影响IL1A的基础分泌，对PTGES2基础分泌影响较小。我们得出结论，LE中的Il1a和Il1rn以及基质中的Il1a、Il1rn和Il1r1受LIF调节，LIF刺激LE顶端分泌IL1A。
