Stimuli through Toll-like receptor (TLR) 3 and 9 affect human chorionic gonadotropin (hCG) production in a choriocarcinoma cell line

Stimuli through Toll-like receptor (TLR) 3 and 9 affect human chorionic gonadotropin (hCG) production in a choriocarcinoma cell line
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DOI:
10.1111/j.1447-0756.2008.00752.x
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发表时间:
2008-04-01
影响因子:
1.6
通讯作者:
Hayakawa, Satoshi
Hayakawa, Satoshi
中科院分区:
医学4区
文献类型:
--
作者:
Komine-Aizawa, Shihoko;Majima, Hiroko;Hayakawa, Satoshi

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目的:Toll样受体(TLR)主要表达于粘膜固有免疫细胞上,其识别微生物相关结构,即所谓的病原体相关分子模式(PAMP)。最近,TLR在胎盘组织中的可能作用,特别是它们在保护孕体免受母体感染的作用,已经被讨论,但TLR在胎盘functions.Methods的生理病理学作用尚未被检查:绒毛膜癌细胞系BeWo被用作滋养层干细胞的模型。首先,使用逆转录-聚合酶链反应研究TLR 1-9在BeWo细胞上的表达。然后,使用人TLR 1 - 9激动剂试剂盒(Pam 3CKS 4、HKLM、Poly(I:C)、大肠杆菌K12脂多糖(LPS)、鼠伤寒沙门氏菌鞭毛蛋白、FSL 1、咪喹莫特、ssRNA 40和ODN 2006),用TLR 1-9激动剂处理细胞。结果:BeWo细胞在Forskolin存在或不存在的情况下,均可组成性表达TLR 1-9 mRNA。TLR 3激动剂Poly(I:C)和TLR 9激动剂CpG-DNA(ODN 2006)上调hCG产生,但在不存在毛喉素的情况下具有最小的作用。与其他TLR激动剂的刺激没有产生显着的增加,无论是在存在或不存在forskolin.Conclusions:TLR 3和TLR 9激动剂上调BeWo细胞hCG的生产。目前的观察结果表明,TLR信号在控制胎盘功能和胚泡-子宫内膜对话,以及在病理生理学,包括不孕症和异位妊娠的替代作用。
Aim: Toll-like receptors (TLR) are expressed mostly on mucosal innate immune cells which recognize microorganism-associated structures, the so called pathogen-associated molecular patterns (PAMP). Recently, possible roles of TLR in placental tissue, especially their role in protecting the conceptus from maternal infection, have been discussed, but the physiopathological roles of TLR in placental functions have yet to be examined.Methods: The choriocarcinoma cell line BeWo was used as a model of trophoblast stem cells. First, the expression of TLR 1-9 on BeWo cells was investigated using reverse transcriptase-polymerase chain reaction. Then, the cells were treated with TLR 1-9 agonists, using the human TLR 1-9 agonist kit (Pam3CKS4, HKLM, Poly (I:C), Escherichia coli K12 lipopolysaccharide (LPS), Salmonella typhimurium flagellin, FSL1, imiquimod, ssRNA 40, and ODN 2006). The concentration of human chorionic gonadotropin (hCG) in the cell culture supernatants was examined on ELISA.Results: BeWo cells constitutively expressed TLR 1-9 mRNA in the presence or absence of forskolin. The TLR 3 agonist, Poly(I:C), and the TLR 9 agonist, CpG-DNA (ODN2006), upregulated hCG production but had minimal effects in the absence of forskolin. Stimulation with the other TLR agonists produced no remarkable increase, whether in the presence or absence of forskolin.Conclusions: TLR 3 and TLR 9 agonists upregulated hCG production in BeWo cells. The present observations suggest alternative roles of TLR signaling in the control of placental functions and blastocyst-endometrial dialogue, as well as in pathophysiology, including for infertility and ectopic pregnancy.