title: Brucella suis vaccine strain S2-infected immortalized caprine endometrial epithelial cell lines induce non-apoptotic ER-stress.
abstract: Brucella, which is regarded as an intracellular pathogen responsible for a zoonotic disease called brucellosis, survives and proliferates within several types of phagocytic and non-phagocytic cells. Brucella infects not only their preferred hosts but also other domestic and wild animal species, inducing abortion and infertility. Therefore, the interaction between uterine cells and Brucella is important for understanding the pathogenesis of this disease. In this study, we describe the Brucella suis vaccine strain S2 (B.suis.S2) infection and replication in the immortalized caprine endometrial epithelial cell line hTERT-EECs and the induced cellular and molecular response modulation in vitro. We found that B.suis S2 was able to infect and replicate to high titers and inhibit the proliferation of EECs and induce non-apoptotic pathways, as determined by B.suis.S2 detection using MTT and acridine orange/ethidium bromide (AO/EB) staining and flow cytometry. We explored the evidence of non-apoptotic pathways using real-time quantitative RT-PCR and by western blot analysis. Finally, we discovered the over-expression of GRP78, ATF4, ATF6, PERK, eIF2α, CHOP, and cytochrome c (Cyt-c) but not IRE1, xbp-1, and caspase-3 in B.suis.S2 (HK)-attacked and B.suis.S2-infected cells, suggesting that the molecular mechanism of ER stress sensor activation by B.suis.S2 is basically concomitant with that by B.suis.S2 (HK) and that ER stress, especially the PERK pathway, plays an important role in the process of B.suis.S2 infecting EEC, which may, in part, explain the role of the uterus in the pathogenesis of B.suis.S2.
authors: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors: Xiangguo
authors: X
authors: Wang
authors: Pengfei
authors: P
authors: Lin
authors: Yanlong
authors: Y
authors: Yin
authors: Jinhua
authors: J
authors: Zhou
authors: Lanjie
authors: L
authors: Lei
authors: Xudong
authors: X
authors: Zhou
authors: Yaping
authors: Y
authors: Jin
authors: Aihua
authors: A
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002004:Brucella Vaccine / Q000276:immunology*; D041021:Brucella suis / Q000276:immunology*; D002006:Brucellosis / Q000517:prevention & control / Q000662:veterinary*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015511:Goat Diseases / Q000517:prevention & control*; D006041:Goats
chemical_list: D002004:Brucella Vaccine; D045304:Cytochromes c; D053148:Caspase 3
references: Cell Microbiol. 2012 Jun;14(6):965-82
references: 22321605
references: MBio. 2013;4(1):e00418-12
references: 23422410
references: J Steroid Biochem Mol Biol. 2013 Nov;138:325-33
references: 23816690
references: Rev Sci Tech. 2013 Apr;32(1):43-51, 53-60
references: 23837364
references: J Infect Dis. 2013 Apr;207(7):1075-83
references: 23303808
references: Biochim Biophys Acta. 2013 Dec;1833(12):3460-70
references: 23850759
references: PLoS Pathog. 2013;9(12):e1003785
references: 24339776
references: Infect Immun. 2000 Jan;68(1):342-51
references: 10603407
references: Mol Cell. 2000 May;5(5):897-904
references: 10882126
references: J Biol Chem. 2002 Apr 5;277(14):12343-50
references: 11805088
references: Vet Microbiol. 2002 Dec 20;90(1-4):165-82
references: 12414142
references: J Exp Med. 2003 Aug 18;198(4):545-56
references: 12925673
references: Cell Death Differ. 2004 Apr;11(4):381-9
references: 14685163
references: Mutat Res. 2005 Jan 6;569(1-2):29-63
references: 15603751
references: Annu Rev Biochem. 2005;74:739-89
references: 15952902
references: J Biochem. 2005 Oct;138(4):501-7
references: 16272146
references: J Biol Chem. 2006 Mar 17;281(11):7260-70
references: 16407291
references: Infect Immun. 2006 May;74(5):2667-75
references: 16622203
references: J Immunol. 2006 May 15;176(10):6245-53
references: 16670335
references: Mol Cell Biol. 2006 Dec;26(24):9220-31
references: 17030611
references: PLoS Pathog. 2008 Jul;4(7):e1000110
references: 18654626
references: Med Microbiol Immunol. 2009 Nov;198(4):221-38
references: 19830453
references: J Biochem. 2010 Apr;147(4):471-83
references: 19919955
references: Int J Syst Evol Microbiol. 2010 Apr;60(Pt 4):801-8
references: 19661515
references: Clin Microbiol Infect. 2011 Sep;17(9):1312-22
references: 21884294
references: Vet Immunol Immunopathol. 2012 Jan 15;145(1-2):248-56
references: 22153993
references: PLoS One. 2012;7(2):e31777
references: 22384074