PMID- 29626977 OWN - NLM STAT- MEDLINE DCOM- 20190130 LR - 20210308 IS - 1532-3102 (Electronic) IS - 0143-4004 (Linking) VI - 64 DP - 2018 Apr TI - IFNtau mediates chemotaxis, motility, metabolism and CK18 downregulation in bovine trophoblast cells in vitro via STAT1 and MAPK42/44 signaling. PG - 17-26 LID - S0143-4004(18)30059-6 [pii] LID - 10.1016/j.placenta.2018.02.004 [doi] AB - INTRODUCTION: IFNtau is the ruminant pregnancy recognition signal. In the study we investigated the autocrine influence of IFNtau on bovine F3 trophoblast cells. In detail chemotaxis, motility, metabolism, cell polarisation (CK18; ezrin) and the underlying classical (STAT1) and non-classical (MAPK42/44) signaling pathways were examined. METHODS: Cellular signaling was analysed by densitometric Western blot (STAT1, MAPK42/44, proteinkinase B) and RT-PCR (IFNAR1, -2). Cellular assays were carried out for chemotaxis (agarose spot assay), cell motility (live cell imaging), metabolism (MTT) and cell polarisation (CK18; ezrin). In vivo-produced conceptuses of gestational days (GD) 20-39 underwent immunohistochemistry (CK18; ezrin) to set the in vitro findings (cell polarisation) in proportion to the in vivo situation. RESULTS: IFNtau (10-1000 ng/ml) mediated dose-dependent effects. 10 ng/ml IFNtau induced chemotaxis and motility, whilst 1000 ng/ml led to reduced chemotaxis, motility and a 92-fold activation of MAPK44. Stimulation of cells with 10-1000 ng/ml IFNtau promoted metabolism (1.4-fold), increased the gene expression of IFNAR1/2 (24 h) and downregulated CK18 but not ezrin. All described in vitro effects were significant. Signaling, motility and metabolism could be blocked by specific inhibitors (PD98059, LY294002). CK18 and ezrin expression patterns in the trophoblast of in vivo conceptuses differed depending on GD. DISCUSSION: IFNtau is a major factor for bovine F3 trophoblast cells and mediates a variety of cellular actions ranging from chemotaxis to polarisation. IFNtau exerts its effects via classical (STAT1) and non-classical (MAPK42/44) signaling pathways in a dose-dependent way. We hypothesize that (dose-dependent) IFNtau regulation of the cellular effects could also be essential for bovine elongation and implantation. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Loch, C AU - Loch C AD - Department of Anatomy, University of Veterinary Medicine Hannover, Germany. FAU - Haeger, J-D AU - Haeger JD AD - Department of Anatomy, University of Veterinary Medicine Hannover, Germany. Electronic address: jan-dirk.haeger@tiho-hannover.de. FAU - Pfarrer, C AU - Pfarrer C AD - Department of Anatomy, University of Veterinary Medicine Hannover, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180221 PL - Netherlands TA - Placenta JT - Placenta JID - 8006349 RN - 0 (Interferon Type I) RN - 0 (Keratin-18) RN - 0 (Pregnancy Proteins) RN - 0 (Receptors, Interferon) RN - 0 (interferon tau) SB - IM MH - Animals MH - Autocrine Communication MH - Cattle MH - Cell Line MH - *Chemotaxis MH - Female MH - Interferon Type I/*physiology MH - Keratin-18/metabolism MH - Pregnancy MH - Pregnancy Proteins/*physiology MH - Receptors, Interferon/metabolism MH - *Signal Transduction MH - Trophoblasts/*physiology OTO - NOTNLM OT - Bovine implantation OT - Bovine trophoblast OT - Cell culture model OT - Interferon tau EDAT- 2018/04/09 06:00 MHDA- 2019/01/31 06:00 CRDT- 2018/04/09 06:00 PHST- 2017/12/22 00:00 [received] PHST- 2018/02/19 00:00 [revised] PHST- 2018/02/19 00:00 [accepted] PHST- 2018/04/09 06:00 [entrez] PHST- 2018/04/09 06:00 [pubmed] PHST- 2019/01/31 06:00 [medline] AID - S0143-4004(18)30059-6 [pii] AID - 10.1016/j.placenta.2018.02.004 [doi] PST - ppublish SO - Placenta. 2018 Apr;64:17-26. doi: 10.1016/j.placenta.2018.02.004. Epub 2018 Feb 21.