PMID- 37342371
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230701
IS  - 2228-5881 (Print)
IS  - 2251-7308 (Electronic)
IS  - 2228-5881 (Linking)
VI  - 13
IP  - 2
DP  - 2023 Mar
TI  - Iron Withdrawal with DIBI, a Novel 3-Hydroxypyridin-4-One Chelator Iron-Binding 
      Polymer, Attenuates Macrophage Inflammatory Responses.
PG  - 368-377
LID - 10.34172/apb.2023.040 [doi]
AB  - Purpose: Iron is an essential trace element for the inflammatory response to 
      infection. In this study, we determined the effect of the recently developed 
      iron-binding polymer DIBI on the synthesis of inflammatory mediators by RAW 264.7 
      macrophages and bone marrow-derived macrophages (BMDMs) in response to 
      lipopolysaccharide (LPS) stimulation. Methods: Flow cytometry was used to 
      determine the intracellular labile iron pool, reactive oxygen species production, 
      and cell viability. Cytokine production was measured by quantitative reverse 
      transcription polymerase chain reaction and enzyme-linked immunosorbent assay. 
      Nitric oxide synthesis was determined by the Griess assay. Western blotting was 
      used to assess signal transducer and activator of transcription (STAT) 
      phosphorylation. Results: Macrophages cultured in the presence of DIBI exhibited 
      a rapid and significant reduction in their intracellular labile iron pool. 
      DIBI-treated macrophages showed reduced expression of proinflammatory cytokines 
      interferon-beta, interleukin (IL)-1beta, and IL-6 in response to LPS. In contrast, 
      exposure to DIBI did not affect LPS-induced expression of tumor necrosis factor-alpha 
      (TNF-alpha). The inhibitory effect of DIBI on IL-6 synthesis by LPS-stimulated 
      macrophages was lost when exogenous iron in the form of ferric citrate was added 
      to culture, confirming the selectivity of DIBI for iron. DIBI-treated macrophages 
      showed reduced production of reactive oxygen species and nitric oxide following 
      LPS stimulation. DIBI-treated macrophages also showed a reduction in 
      cytokine-induced activation of STAT 1 and 3, which potentiate LPS-induced 
      inflammatory responses. Conclusion: DIBI-mediated iron withdrawal may be able to 
      blunt the excessive inflammatory response by macrophages in conditions such as 
      systemic inflammatory syndrome.
CI  - (c)2023 The Authors.
FAU - Ghassemi-Rad, Javad
AU  - Ghassemi-Rad J
AUID- ORCID: 0000-0001-7812-2401
AD  - Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova 
      Scotia B3H 4R2, Canada.
FAU - Fernando, Wasundara
AU  - Fernando W
AD  - Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova 
      Scotia B3H 4R2, Canada.
FAU - Holbein, Bruce E
AU  - Holbein BE
AD  - Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie 
      University, Halifax, Nova Scotia B3H 4R2, Canada.
FAU - Hoskin, David W
AU  - Hoskin DW
AUID- ORCID: 0000-0001-9012-0177
AD  - Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova 
      Scotia B3H 4R2, Canada.
AD  - Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie 
      University, Halifax, Nova Scotia B3H 4R2, Canada.
AD  - Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, Nova 
      Scotia B3H 4R2, Canada.
LA  - eng
PT  - Journal Article
DEP - 20220102
PL  - Iran
TA  - Adv Pharm Bull
JT  - Advanced pharmaceutical bulletin
JID - 101578021
PMC - PMC10278213
OTO - NOTNLM
OT  - Cytokines
OT  - Inflammation
OT  - Iron
OT  - Macrophages
OT  - Reactive oxygen species
OT  - Signal transduction
COIS- BEH has a beneficial interest in Chelation Partners Inc. The other authors 
      declare that they have no conflict of interests.
EDAT- 2023/06/21 13:04
MHDA- 2023/06/21 13:05
PMCR- 2022/01/02
CRDT- 2023/06/21 12:00
PHST- 2021/06/02 00:00 [received]
PHST- 2021/10/29 00:00 [revised]
PHST- 2021/12/31 00:00 [accepted]
PHST- 2023/06/21 13:05 [medline]
PHST- 2023/06/21 13:04 [pubmed]
PHST- 2023/06/21 12:00 [entrez]
PHST- 2022/01/02 00:00 [pmc-release]
AID - 10.34172/apb.2023.040 [doi]
PST - ppublish
SO  - Adv Pharm Bull. 2023 Mar;13(2):368-377. doi: 10.34172/apb.2023.040. Epub 2022 Jan 
      2.