Roles of gamma interferon and tumor necrosis factor-alpha in shiga toxin lethality. 2002

Sanae Sasaki, and Katsuhiko Omoe, and Yoh ichi Tagawa, and Yoichiro Iwakura, and Kenji Sekikawa, and Kunihiro Shinagawa, and Akio Nakane
Department of Bacteriology, Hirosaki University School of Medicine, Hirosaki, Japan.

Shiga toxins (Stxs) have been specifically implicated as a causal factor of hemolytic uremic syndrome and acute encephalopathy. The first step of Stx-induced brain damage is considered to injure endothelial cells cooperating with tumor necrosis factor-alpha (TNF-alpha). Gamma interferon (IFN-gamma) is one of the proinflammatory cytokines as well as TNF-alpha is critical in activation of endothelial cells. Therefore we focused on the possibility of IFN-gamma-mediated lethality of Stx1 or Stx2 in mice. All of mice died within 3-4 days after injection with 400 ng of Stx1 and 37.5% of mice, which had been injected with 133 ng, survived. In contrast, a lethal dose of Stx2 was 40 times lower than that of Stx1. When mice were given 400 ng of Stx1 or 10 ng of Stx2, IFN-gamma mRNA was detected in the spleens 24h after injection. Moreover, when mice were injected with 133 ng of Stx1 or 3.3 ng of Stx2, survival rates of IFN-gamma-deficient mice and TNF-alpha-deficient mice were significantly higher than that of wild-type mice. The present study using cytokine-gene knockout mice directly demonstrated that not only TNF-alpha but also IFN-gamma is involved in lethality of Stx1 and Stx2.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D022622 Shiga Toxin 1 A toxin produced by certain pathogenic strains of ESCHERICHIA COLI such as ESCHERICHIA COLI O157. It is closely related to SHIGA TOXIN produced by SHIGELLA DYSENTERIAE. SLT-I,SLTI,Shiga-Like Toxin I,Stx1 Protein,VT1 Cytotoxin,Vero Cytotoxin VT1,Verocytotoxin 1,Verotoxin I,Protein, Stx1,SLT I,Shiga Like Toxin I
D022641 Shiga Toxin 2 A toxin produced by certain pathogenic strains of ESCHERICHIA COLI such as ESCHERICHIA COLI O157. It shares 50-60% homology with SHIGA TOXIN and SHIGA TOXIN 1. SLT-II,SLTII,Shiga Like Toxin II,Shiga Toxin 2, Escherichia coli,Shiga-Like Toxin II,Stx2 protein,VT2 Cytotoxin,Vero Cytotoxin VT2,Verotoxin 2,Cytotoxin, VT2,SLT II
D023421 Models, Animal Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing. Experimental Animal Models,Laboratory Animal Models,Animal Model,Animal Model, Experimental,Animal Model, Laboratory,Animal Models,Animal Models, Experimental,Animal Models, Laboratory,Experimental Animal Model,Laboratory Animal Model,Model, Animal,Model, Experimental Animal,Model, Laboratory Animal,Models, Experimental Animal,Models, Laboratory Animal

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