title: Hypoxia-inducible factor 1-regulated lysyl oxidase is involved in Staphylococcus aureus abscess formation.
abstract: Hypoxia-inducible factor 1 (HIF-1) is the key transcription factor involved in the adaptation of mammals to hypoxia and plays a crucial role in cancer angiogenesis. Recent evidence suggests a leading role for HIF-1 in various inflammatory and infectious diseases. Here we describe the role of HIF-1 in Staphylococcus aureus infections by investigating the HIF-1-dependent host cell response. For this purpose, transcriptional profiling of HIF-1α-deficient HepG2 and control cells, both infected with Staphylococcus aureus, was performed. Four hours after infection, the expression of 190 genes, 24 of which were regulated via HIF-1, was influenced. LOX (encoding lysyl oxidase) was one of the upregulated genes with a potential impact on the course of S. aureus infection. LOX is an amine oxidase required for biosynthetic cross-linking of extracellular matrix components. LOX was upregulated in vitro in different cell cultures infected with S. aureus and also in vivo, in kidney abscesses of mice intravenously infected with S. aureus and in clinical skin samples from patients with S. aureus infections. Inhibition of LOX by β-aminopropionitrile (BAPN) did not affect the bacterial load in kidneys or blood but significantly influenced abscess morphology and collagenization. Our data provide evidence for a crucial role of HIF-1-regulated LOX in abscess formation.
authors: Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Klinikum der Goethe-Universität, Frankfurt am Main, Germany.
authors: Christiane
authors: C
authors: Beerlage
authors: Jessica
authors: J
authors: Greb
authors: Dorothee
authors: D
authors: Kretschmer
authors: Mohammad
authors: M
authors: Assaggaf
authors: Philip C
authors: PC
authors: Trackman
authors: Martin-Leo
authors: ML
authors: Hansmann
authors: Michael
authors: M
authors: Bonin
authors: Johannes A
authors: JA
authors: Eble
authors: Andreas
authors: A
authors: Peschel
authors: Bernhard
authors: B
authors: Brüne
authors: Volkhard A J
authors: VA
authors: Kempf
mesh_terms: D000038:Abscess / Q000382:microbiology* / Q000473:pathology; D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000382:microbiology / Q000473:pathology; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology*
chemical_list: D016326:Extracellular Matrix Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C077112:Lox protein, mouse; D000629:Aminopropionitrile; D008249:Protein-Lysine 6-Oxidase
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