Journal article
Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice
PloS one, Vol.8(11), e78850
2013
Abstract
Chronic intestinal inflammation and high dietary iron are associated with colorectal cancer development. The role of Stat3 activation in iron-induced colonic inflammation and tumorigenesis was investigated in a mouse model of inflammation-associated colorectal cancer. Mice, fed either an iron-supplemented or control diet, were treated with azoxymethane and dextran sodium sulfate (DSS). Intestinal inflammation and tumor development were assessed by endoscopy and histology, gene expression by real-time PCR, Stat3 phosphorylation by immunoblot, cytokines by ELISA and apoptosis by TUNEL assay. Colonic inflammation was more severe in mice fed an iron-supplemented compared with a control diet one week post-DSS treatment, with enhanced colonic IL-6 and IL-11 release and Stat3 phosphorylation. Both IL-6 and ferritin, the iron storage protein, co-localized with macrophages suggesting iron may act directly on IL-6 producing-macrophages. Iron increased DSS-induced colonic epithelial cell proliferation and apoptosis consistent with enhanced mucosal damage. DSS-treated mice developed anemia that was not alleviated by dietary iron supplementation. Six weeks post-DSS treatment, iron-supplemented mice developed more and larger colonic tumors compared with control mice. Intratumoral IL-6 and IL-11 expression increased in DSS-treated mice and IL-6, and possibly IL-11, were enhanced by dietary iron. Gene expression of iron importers, divalent metal transporter 1 and transferrin receptor 1, increased and iron exporter, ferroportin, decreased in colonic tumors suggesting increased iron uptake. Dietary iron and colonic inflammation synergistically activated colonic IL-6/IL-11-Stat3 signaling promoting tumorigenesis. Oral iron therapy may be detrimental in inflammatory bowel disease since it may exacerbate colonic inflammation and increase colorectal cancer risk.
Details
- Title
- Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice
- Authors/Creators
- A.C.G. Chua (Author/Creator)B.R.S. Klopcic (Author/Creator)D.S. Ho (Author/Creator) - Western Australian Institute for Medical Research Perth, Western Australia, AustraliaS.K. Fu (Author/Creator) - Fremantle HospitalC.H. Forrest (Author/Creator) - The University of Western AustraliaK.D. Croft (Author/Creator) - Royal Perth HospitalJ.K. Olynyk (Author/Creator) - Curtin UniversityI.C. Lawrance (Author/Creator) - Fremantle HospitalD. Trinder (Author/Creator) - Western Australian Institute for Medical Research Perth, Western Australia, Australia
- Publication Details
- PloS one, Vol.8(11), e78850
- Publisher
- Public Library of Science
- Identifiers
- 991005544477707891
- Copyright
- 2013 Chua et al.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
114 File views/ downloads
48 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.184 Physiology & Metals
- 1.184.573 Iron Metabolism
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine