Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation contributes to the development of papillomas and squamous cell carcinomas in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-l3-acetate (TPA) model of skin carcinogenesis. Synthetic oligonucleotides (ODN) containing repetitive TTAGGG motifs have been shown to block deleterious inflammatory reactions in murine models of autoimmunity, pneumonitis, and shock. This article examines whether treatment with suppressive (Sup) ODN can interfere with DMBA/TPA-induced inflammation, thereby reducing papilloma formation. Results indicate that Sup ODN block TPA-dependent skin hyperplasia, edema, and leukocytic infiltration. Sup ODN also inhibit the upregulation of genes encoding pro-oncogenic chemokines and other markers of inflammation including CXCL2, CCL2, COX-2, and ODC (ornithine decarboxylase). Of greatest import, Sup ODN reduce papilloma formation in a dose- and sequence-dependent manner. These findings suggest that Sup ODN may provide a novel means of preventing inflammation and associated oncogenesis.
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PMID:Effect of suppressive oligodeoxynucleotides on the development of inflammation-induced papillomas. 2136 57

We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2 (-/-) mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. We now bred Arg2 (-/-) to Nos2 (-/-) mice, and infected them with H. pylori. Compared to wild-type mice, both Arg2 (-/-) and Arg2 (-/-) ;Nos2 (-/-) mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While Arg2 (-/-) mice demonstrated enhanced M1 macrophage activation, Nos2 (-/-) and Arg2 (-/-) ;Nos2 (-/-) mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from Arg2 (-/-), but not Nos2 (-/-) or Arg2 (-/-) ;Nos2 (-/-) mice. Gastric tissues from infected Arg2 (-/-) mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine N (1)-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during H. pylori infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of H. pylori by restricting M1 macrophage activation and polyamine metabolism.
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PMID:Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection. 2707 21