Macrophage-inflammatory protein-3alpha/CCL-20 is transcriptionally induced by the iron chelator desferrioxamine in human mononuclear phagocytes through nuclear factor (NF)-kappaB

Molecular Immunology
L VaresioM C Bosco

Abstract

Alterations in iron availability can trigger pro-inflammatory signals in various cell types. We demonstrate that desferrioxamine (DFX), an iron chelator used in clinics for the treatment of iron overload, neoplasias, and Alzheimer disease, stimulates the expression and secretion of CCL20, a chemoattractant for immature dendritic cells, activated/memory T lymphocytes, and naive B cells, in primary human monocytes and monocyte-derived macrophages. Iron chelation was part of the mechanism by which DFX induced CCL20, because addition of iron sulfate counteracted its stimulatory effects. Functional studies of the CCL20 promoter, using a series of 5'-deleted and mutated reporter constructs, demonstrated that CCL20 mRNA induction was dependent on gene transcription activation and mediated by the NF-kappaB pathway. The NF-kappaB element located at position -92/-82 of the CCL20 promoter was required for gene transactivation by DFX because: (i) transcription was abrogated by a 3bp mutation of the NF-kappaB-binding motif; (ii) treatment with DFX increased specific NF-kappaB binding to this sequence. Nuclear translocation of both NF-kappaBp65 and NF-kappaBp50 family members was increased in response to DFX and associated with I-kappaBalpha...Continue Reading

References

Nov 24, 1992·Biochemistry·R R Crichton, R J Ward
Jan 1, 1992·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·P A SeligmanE W Gelfand
Oct 1, 1995·Immunology Today·G WeissD Fuchs
Dec 1, 1994·Current Opinion in Immunology·T J Schall, K B Bacon
Feb 17, 1995·The Journal of Biological Chemistry·R LinJ Hiscott
Mar 1, 1995·Scandinavian Journal of Immunology·S Golding, S P Young
Jun 1, 1993·Trends in Microbiology·C L BaldwinD M Fernandes
Jan 1, 1993·Clinical Pharmacology and Therapeutics·T P KruckD R McLachlan
Jan 1, 1996·Acta Haematologica·A DonfrancescoA Castellano
Dec 16, 1998·The Journal of Laboratory and Clinical Medicine·A R O'Brien-LadnerL J Wesselius
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M C BoscoL Varesio
Mar 22, 2000·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·T A HamiltonR Kishore
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·E SchutyserJ Van Damme
Oct 29, 2000·British Journal of Haematology·A ScaccabarozziS Fargion
Apr 2, 2002·Gynecologic Oncology·Thierry SimonartRobert Snoeck
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
May 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shinichi SugitaToshifumi Matsuyama
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Annamaria RapellaMaria Carla Bosco
Aug 28, 2002·Biochemical Society Transactions·R J WardR R Crichton
Oct 29, 2002·Best Practice & Research. Clinical Haematology·J J M Marx
Jun 25, 2003·Biochemical and Biophysical Research Communications·Hyun-Ja JeongHyung-Min Kim
Jul 30, 2003·Journal of Leukocyte Biology·Horst OexleGünter Weiss
Sep 2, 2003·Cytokine & Growth Factor Reviews·Evemie SchutyserJo Van Damme
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria Carla BoscoLuigi Varesio
Jul 2, 2004·Nature Reviews. Cancer·Fran Balkwill
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert D StoutJill Suttles
Mar 11, 2006·Biochemical and Biophysical Research Communications·Kyung Jin WooTaeg Kyu Kwon
Jul 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria Carla BoscoLuigi Varesio
Oct 31, 2006·Oncogene·M S HaydenS Ghosh
Mar 10, 2007·International Journal of Immunopathology and Pharmacology·B ManzariL Varesio
May 20, 2008·Journal of Alzheimer's Disease : JAD·Eugene D Weinberg, Judith Miklossy
May 31, 2008·Journal of Tissue Engineering and Regenerative Medicine·Esther PotierHervé Petite

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Citations

Aug 17, 2016·International Journal of Molecular Sciences·Ya LiHua-Bin Li
Sep 7, 2016·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Andrew J Ghio
Feb 10, 2012·Glia·Gordon P MearesEtty N Benveniste
Aug 13, 2020·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Feb 13, 2016·Cellular Microbiology·Anna-Maria MitterstillerGuenter Weiss
Oct 8, 2020·Journal of Medicinal Chemistry·Xiaoying JiangYuanyuan Xie

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