Deferoxamine B but not deferoxamine G1 inhibits cytokine production in murine bone marrow macrophages.
The iron chelator deferoxamine (DFO) B enhances virulence of Yersinia enterocolitica and modulates cellular immune responses. Since cytokines mediate effector mechanisms in resolution of yersiniae from infected tissues, the impact of DFO B and DFO G1 on cytokine production by murine bone marrow macrophages (BMM) was investigated. BMM were stimulated with lipopolysaccharide (LPS) of Salmonella typhimurium or infected with Y. enterocolitica. DFO B inhibited interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-alpha mRNA production 4-fold (shown by semiquantitative reverse transcription polymerase chain reaction). TNF-alpha and IL-6 protein production was reduced 50% by DFO B. In contrast, DFO G1 had no effect on cytokine production. Moreover, cytokine production by Yersinia-infected BMM was decreased by plasmid-encoded Yersinia proteins. Thus, plasmid-cured strains induced higher cytokine responses in BMM than did the wild type strain. These results suggest that DFO B acts in a bimodal fashion in yersiniosis: iron supply to the pathogen and immunosuppression of the host.
Autenrieth
I B
IB
Institut für Hygiene und Mikrobiologie, Universität Würzburg, Germany.
Bohn
E
E
Ewald
J H
JH
Heesemann
J
J
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002712:Chlorides; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D007502:Iron Chelating Agents / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015008:Yersinia enterocolitica / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity
D000199:Actins; D002712:Chlorides; D016207:Cytokines; D005290:Ferric Compounds; D007378:Interleukins; D007502:Iron Chelating Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C094778:deferoxamine G1; C002577:ferrioxamine B; D003676:Deferoxamine; C024555:ferric chloride