title: Shiga Toxins Trigger the Secretion of Lysyl-tRNA Synthetase to Enhance Proinflammatory Responses.
abstract: Shiga toxins (Stxs) produced by Shiga toxin-producing Escherichia coli (STEC) strains are major virulence factors that cause fatal systemic complications, such as hemolytic uremic syndrome and disruption of the central nervous system. Although numerous studies report proinflammatory responses to Stx type 1 (Stx1) or Stx type 2 (Stx2) both in vivo and in vitro, none have examined dynamic immune regulation involving cytokines and/or unknown inflammatory mediators during intoxication. Here, we showed that enzymatically active Stxs trigger the dissociation of lysyl-tRNA synthetase (KRS) from the multi-aminoacyl-tRNA synthetase complex in human macrophage-like differentiated THP-1 cells and its subsequent secretion. The secreted KRS acted to increase the production of proinflammatory cytokines and chemokines. Thus, KRS may be one of the key factors that mediate transduction of inflammatory signals in the STEC-infected host.
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Moo-Seung
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.|Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Haenaem
authors.initials: H
authors.lastname: Kwon
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.|Department of Biochemistry, Chungnam National University, Daejeon 34134, Republic of Korea.
authors.forename: Loi T
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 34134, Republic of Korea.
authors.forename: Chan Yong
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019453:Escherichia coli O157 / Q000235:genetics; D006801:Humans; D008250:Lysine-tRNA Ligase / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D022603:Shiga Toxins / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D054323:Shiga-Toxigenic Escherichia coli
chemical_list: D018925:Chemokines; D016207:Cytokines; D022603:Shiga Toxins; D000604:Amino Acyl-tRNA Synthetases; D008250:Lysine-tRNA Ligase
keywords: Human lysyl-tRNA synthetase; Proinflammatory mediator; Shiga toxin