Molecular mechanism for the effects of E. coli heat-labile enterotoxin on mouse embryo survival

Wenyan Li; Dongmei Han; Shuang Liang; Zhenyu Zhong; Xiujin Li; Jiexia Wen; Hongyu Lin; Liyue Wang; Xiangyun Li; Xiuhui Zhong; Fei Zhong

doi:10.1016/j.reprotox.2014.01.005

Molecular mechanism for the effects of E. coli heat-labile enterotoxin on mouse embryo survival

Reprod Toxicol. 2014 Jun:45:31-8. doi: 10.1016/j.reprotox.2014.01.005. Epub 2014 Jan 17.

Authors

Wenyan Li¹, Dongmei Han², Shuang Liang³, Zhenyu Zhong⁴, Xiujin Li⁵, Jiexia Wen², Hongyu Lin⁵, Liyue Wang², Xiangyun Li⁶, Xiuhui Zhong², Fei Zhong⁷

Affiliations

¹ 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.
² 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.
³ Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
⁴ Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
⁵ Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004, China.
⁶ Laboratory of Genetics and Animal Breeding, College of Animal Science and Technology, Agricultural University of Hebei, Baoding 071001, China.
⁷ 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.

PMID: 24440567
DOI: 10.1016/j.reprotox.2014.01.005

Abstract

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.

Keywords: Cytokines; E. coli heat-labile enterotoxin; Embryo survival; Inflammasome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Toxins / toxicity*
Carrier Proteins / immunology
Cell Line
Cytokines / blood
Cytokines / immunology
Embryo Loss / chemically induced
Embryo Loss / immunology
Embryo, Mammalian / drug effects*
Embryo, Mammalian / immunology
Enterotoxins / toxicity*
Escherichia coli Proteins / toxicity*
Female
Inflammasomes / drug effects
Interleukin-1beta / immunology
Lipopolysaccharides
Macrophages / drug effects
Mice, Inbred ICR
NLR Family, Pyrin Domain-Containing 3 Protein
Placenta / immunology
Pregnancy
Recombinant Proteins / toxicity
Th1 Cells / drug effects
Th1 Cells / immunology
Th2 Cells / drug effects
Th2 Cells / immunology

Substances

Bacterial Toxins
Carrier Proteins
Cytokines
Enterotoxins
Escherichia coli Proteins
Inflammasomes
Interleukin-1beta
Lipopolysaccharides
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse
Recombinant Proteins
heat-labile enterotoxin, E coli