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

Chua, A.C.G., Klopcic, B., Ho, D., Olynyk, J.K., Lawrance, I.C. and Trinder, D. (2011) Colonic interleukin-6 expression is induced by intestinal inflammation and dietary iron. Journal of Gastroenterology and Hepatology, 26 (Supp. 4). p. 17.

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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.

Publication Type: Journal Article
Notes: Abstract from the Australian Gastroenterology Week 2011, Brisbance Convention and Exhibition Centre, 12 - 15 September 2011
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