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Colonic interleukin-6 expression is induced by intestinal inflammation and dietary iron
Journal article   Peer reviewed

Colonic interleukin-6 expression is induced by intestinal inflammation and dietary iron

A.C.G. Chua, B. Klopcic, D. Ho, J.K. Olynyk, I.C. Lawrance and D. Trinder
Journal of Gastroenterology and Hepatology, Vol.26(Supp. 4)
2011
DOI: https://doi.org/10.1111/j.1440-1746.2011.06820.x
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Abstract

Chronic intestinal inflammation and high dietary iron are associated with a greater risk of developing colorectal cancer. The aim of this study was to investigate the role of IL-6 in iron-induced colonic inflammation and tumourigenesis in a mouse model of colorectal cancer. Methods: Mice, fed either an iron-supplemented (1% carbonyl iron) or control (0.01% iron) diet, were treated with dextran sodium sulphate (DSS) and azoxymethane (AOM) to induce intestinal inflammation and cancer. Intestinal inflammation and tumour development were assessed using high-resolution video endoscopy at multiple time-points. Colonic inflammation and tumours were examined histologically and gene expression by real-time PCR. Results: Seven days post-AOM/DSS treatment, intestinal inflammation was more severe in iron-loaded mice (p < 0.05). Colonic pro-inflammatory cytokines, IL-6, IFN-γ and TNFα gene expression increased with AOM/ DSS treatment confirming the presence of intestinal inflammation (p < 0.05). Dietary iron loading had an additive effect on the gene expression of IL-6 and other members of this family, IL-11 and IL-17a, in AOM/ DSS-treated mice. STAT3 phosphorylation was increased in AOM/DSS treated mice and this was further enhanced with dietary iron loading. Five weeks after AOM/DSS treatment, iron-loaded mice developed a greater number and larger-sized colonic tumours compared to control mice (p < 0.05). Dietary iron-loading also induced an additive effect on tumour IL-6 gene expression in AOM/DSS-treated mice (p < 0.05). Expression of cellular iron import genes DMT1, Zip14a and Tfr1 was increased and cellular export gene ferroportin was reduced in colonic tumours compared to non-tumour tissue from the same animal (p < 0.05), suggesting increased iron uptake by tumours may promote growth. Summary/Conclusions: Dietary iron-loading promoted colonic inflammation and tumour formation. The mechanistic basis for the interaction between iron, inflammation and colorectal cancer may involve IL-6/ STAT3 signalling.

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