title: Anakinra and etanercept prevent embryo loss in pregnant nonobese diabetic mice.
abstract: Bacteria and viruses activate the host innate immune response via Toll-like receptor (TLR)-involved signaling and potentially cause pregnancy failure. TLR7 and TLR9 respond to single-stranded RNA (a viral intermediate) and hypomethylated CpG DNA motifs (specific molecular constituents of bacteria) respectively. In this study, we treated murine RAW264.7 cells with R837, CpG1826, or a combination of the two. RT-PCR was performed to detect cytokines, Tlr7, and Tlr9. WT and nonobese diabetic murine embryo resorption models were established by i.p. injections of TLR7 and TLR9 ligands. Neutralizing antibodies and the IL1β and TNFα inhibitors were used. The specific inhibitors anakinra and etanercept effectively prevented TLR7 and TLR9 ligand-induced embryo loss. Notably, this effect was not observed in decidual NK cell-depleted mice. Our findings suggest that anakinra and etanercept may have potential for preventing TLR7 or TLR9 ligand-induced abortion in the presence of decidual NK cells.
authors.affiliation: Reproductive Medicine CenterRenmin Hospital of Wuhan University, Wuhan 430060, ChinaSchool of MedicineInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Reproductive Medicine CenterRenmin Hospital of Wuhan University, Wuhan 430060, ChinaSchool of MedicineInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Reproductive Medicine CenterRenmin Hospital of Wuhan University, Wuhan 430060, ChinaSchool of MedicineInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Qingzhen
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Reproductive Medicine CenterRenmin Hospital of Wuhan University, Wuhan 430060, ChinaSchool of MedicineInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Reproductive Medicine CenterRenmin Hospital of Wuhan University, Wuhan 430060, ChinaSchool of MedicineInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Fuju
authors.initials: F
authors.lastname: Tian
authors.affiliation: Reproductive Medicine CenterRenmin Hospital of Wuhan University, Wuhan 430060, ChinaSchool of MedicineInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China Dryangjing108@163.com wangmingxu118@163.com.
authors.forename: Wangming
authors.initials: W
authors.lastname: Xu
authors.affiliation: Reproductive Medicine CenterRenmin Hospital of Wuhan University, Wuhan 430060, ChinaSchool of MedicineInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China Dryangjing108@163.com wangmingxu118@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D020964:Embryo Loss / Q000378:metabolism / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D012333:RNA, Messenger; D000068800:Etanercept