ABSTRACT
Objective: Inflammatory bowel diseases (IBD) are complex disorders. Iron accumulates in the inflamed tissue of IBD patients, yet neither a mechanism for the accumulation nor its implication on the course of inflammation are known. We hypothesized that the inflammation modifies iron homeostasis, affects tissue iron distribution and that this in turn perpetuates the inflammation. Design: This study analyzed human biopsies, animal models and cellular systems to decipher the role of iron homeostasis in IBD. Results: We found inflammation-mediated modifications of iron distribution, and iron-decoupled activation of the iron regulatory protein (IRP)1. To understand the role of IRP1 in the course of this inflammation-associated iron pattern, a novel cellular co-culture model was established, that replicated the iron-pattern observed in vivo, and supported involvement of nitric oxide in the activation of IRP1 and the typical iron pattern in inflammation. Importantly, deletion of IRP1 from an IBD mouse model completely abolished both, the misdistribution of iron and intestinal inflammation. Conclusion: These findings suggest that IRP1 plays a central role in the coordination of the inflammatory response in the intestinal mucosa and that it is a viable candidate for therapeutic intervention in IBD.
ABSTRACT
We investigated the association between iron status, B12, and inflammatory markers among 101 adolescent girls. We found that B12 showed significant negative association with tumor necrosis factor-alpha (TNF-α) (rs = -0.232, P = 0.020) and positive association with serum ferritin (SF) (rs = 0.209, P = 0.036) among girls. Our results showed that hepcidin discriminates anemic and non-anemic population under normal B12 conditions. The logistic regression analysis revealed that the risk of having higher TNF-α levels was 13.2 times higher in low B12 girls in the presence of anemia compared to the girls having normal hemoglobin and B12 levels.
