Molecular mechanism for the effects of E. coli heat-labile enterotoxin on mouse embryo survival.
Heat-labile enterotoxin (LT) can cause animal enteritis and diarrhea. However, the possible association of LT with embryo survival in pregnant animals and the mechanisms involved remain unknown. To investigate the effects of LT on embryo survival, we treated mouse early embryos in vitro and pregnant mice in vivo with recombinant LT. LT significantly decreased mouse embryo survival, and induced IFN-γ, IL-2 and IL-1β production in the serum and placental tissue. LT also triggered IL-1β release from LPS-primed microphages, suggesting LT can activate inflammasomes. To determine the pathway involved in LT-induced inflammasome activation, small interfering RNAs were used to knockdown NLRP3 and ASC, the key components of NLRP3 inflammasome pathway. Ablation of NLRP3 and ASC abolished LT-induced IL-1β release, confirming the involvement of NLRP3 inflammasome. By comparing two subunits of LT, only LTA but not LTB subunit was identified to activate the NLRP3 inflammasome.
Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China; Hebei Engineering and Technology Research Center of Veterinary Biotechnology , Baoding 071001, China; Department of Biology, College of Basic Medicine, Hebei University, Baoding 071000, China.
Wenyan
W
Li
Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China; Hebei Engineering and Technology Research Center of Veterinary Biotechnology , Baoding 071001, China.
Dongmei
D
Han
Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Shuang
S
Liang
Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Zhenyu
Z
Zhong
Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004, China.
Xiujin
X
Li
Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China; Hebei Engineering and Technology Research Center of Veterinary Biotechnology , Baoding 071001, China.
Jiexia
J
Wen
Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004, China.
Hongyu
H
Lin
Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China; Hebei Engineering and Technology Research Center of Veterinary Biotechnology , Baoding 071001, China.
Liyue
L
Wang
Laboratory of Genetics and Animal Breeding, College of Animal Science and Technology, Agricultural University of Hebei, Baoding 071001, China.
Xiangyun
X
Li
Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China; Hebei Engineering and Technology Research Center of Veterinary Biotechnology , Baoding 071001, China.
Xiuhui
X
Zhong
Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China; Hebei Engineering and Technology Research Center of Veterinary Biotechnology , Baoding 071001, China. Electronic address: feizhong2000@yahoo.com.
Fei
F
Zhong
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002352:Carrier Proteins / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000097:blood / Q000276:immunology; D020964:Embryo Loss / Q000139:chemically induced / Q000276:immunology; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000276:immunology; D004768:Enterotoxins / Q000633:toxicity*; D029968:Escherichia coli Proteins / Q000633:toxicity*; D005260:Female; D058847:Inflammasomes / Q000187:drug effects; D053583:Interleukin-1beta / Q000276:immunology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D008813:Mice, Inbred ICR; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D011994:Recombinant Proteins / Q000633:toxicity; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D001427:Bacterial Toxins; D002352:Carrier Proteins; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D011994:Recombinant Proteins; C027538:heat-labile enterotoxin, E coli
Cytokines; E. coli heat-labile enterotoxin; Embryo survival; Inflammasome